2022/06/28 更新

写真a

サワムラ ナオヤ
澤村 直哉
所属
研究院(研究機関) ナノ・ライフ創新研究機構
職名
上級研究員(研究院教授)

兼担

  • 理工学術院   先進理工学部

  • 国際学術院   国際教養学部

学歴

  •  
    -
    2000年

    東京大学   医学系研究科   脳神経医学  

  •  
    -
    1996年

    筑波大学   医科学研究科   医科学  

  •  
    -
    1994年

    東京理科大学   理工学部   応用生物科学科  

学位

  • 東京大学   博士(医学)

経歴

  • 2013年04月
    -
     

    早稲田大学 理工学術院 准教授

  • 2009年04月
    -
     

    早稲田大学 理工学術院 研究院准教授

  • 2008年10月
    -
     

    早稲田大学 先端科学・健康医療融合研究機構、生命医療工学研究所 准教授

  • 2006年07月
    -
     

    早稲田大学 先端科学・健康医療融合研究機構、生命医療工学研究所 講師

  • 2003年03月
    -
    2005年03月

    日本学術振興会 海外特別研究員

  • 2003年03月
    -
     

    ジョンズホプキンス大学医学部 精神医学部門、Postdoctoral Fellow

  • 2002年04月
    -
    2003年02月

    日本学術振興会 科学技術特別研究員

  • 2001年01月
    -
    2002年03月

    科学技術振興事業団 科学技術特別研究員

  • 2000年04月
    -
    2000年12月

    長寿科学振興財団 リサーチレジデント

  • 2000年04月
    -
     

    国立長寿医療研究センター 痴呆疾患研究部 臨床研究室

▼全件表示

所属学協会

  •  
     
     

    日本神経化学会

  •  
     
     

    日本進化学会

 

研究分野

  • 神経科学一般

研究キーワード

  • 神経化学、神経変性疾患、統合失調症、精神疾患、アルツハイマー病、発達障害、ミトコンドリア、分子進化

論文

  • Proliferation and differentiation of primary bovine myoblasts using Chlorella vulgaris extract for sustainable production of cultured meat.

    Yuta Okamoto, Yuji Haraguchi, Azumi Yoshida, Hironobu Takahashi, Kumiko Yamanaka, Naoya Sawamura, Toru Asahi, Tatsuya Shimizu

    Biotechnology progress     e3239  2022年01月  [国際誌]

     概要を見る

    Recently, cultured meat obtained from livestock-derived cells is being considered as a sustainable food source that reduces the use of natural resources. This study aimed to show that nutrients extracted from Chlorella vulgaris were beneficial in the culture of primary bovine myoblasts (PBMs), a major cell source for cultured meat production. Nutrients (glucose, amino acids, and vitamins) present in the animal-cell culture media were effectively recovered from C. vulgaris using acid hydrolysis treatment. On culture in nutrient-free inorganic salt solution, cell death was induced in most PBMs after 6 days of cultivation. However, the addition of C. vulgaris extract (CVE) significantly improved PBM viability, which was comparable to the viability in conventional culture medium (Dulbecco's modified Eagle's medium). Furthermore, by adding horse serum to induce differentiation, the formation of myotubes was confirmed when CVE were used. Together, the results showed that CVE could be used as an alternative to the conventional culture medium for PBMs. These findings will not only lower the environmental risks associated with the establishment of this eco-friendly cell culture system, but also highlight microalgae as a potent nutrient source that can replace conventional grain-dependent nutrient sources.

    DOI PubMed

  • Rapid evolution of mammalian APLP1 as a synaptic adhesion molecule.

    Wataru Onodera, Toru Asahi, Naoya Sawamura

    Scientific reports   11 ( 1 ) 11305 - 11305  2021年05月  [査読有り]  [国際誌]

    担当区分:責任著者

     概要を見る

    Amyloid precursor protein (APP) family members are involved in essential neuronal development including neurite outgrowth, neuronal migration and maturation of synapse and neuromuscular junction. Among the APP gene family members, amyloid precursor-like protein 1 (APLP1) is selectively expressed in neurons and has specialized functions during synaptogenesis. Although a potential role for APLP1 in neuronal evolution has been indicated, its precise evolutionary and functional contributions are unknown. This study shows the molecular evolution of the vertebrate APP family based on phylogenetic analysis, while contrasting the evolutionary differences within the APP family. Phylogenetic analysis showed 15 times higher substitution rate that is driven by positive selection at the stem branch of the mammalian APLP1, resulting in dissimilar protein sequences compared to APP/APLP2. Docking simulation identified one positively selected site in APLP1 that alters the heparin-binding site, which could affect its function, and dimerization rate. Furthermore, the evolutionary rate covariation between the mammalian APP family and synaptic adhesion molecules (SAMs) was confirmed, indicating that only APLP1 has evolved to gain synaptic adhesion property. Overall, our results suggest that the enhanced synaptogenesis property of APLP1 as one of the SAMs may have played a role in mammalian brain evolution.

    DOI PubMed

  • Cereblon-mediated degradation of the amyloid precursor protein via the ubiquitin-proteasome pathway.

    Tomotaka Kurihara, Toru Asahi, Naoya Sawamura

    Biochemical and biophysical research communications    2020年01月  [査読有り]  [国際誌]

    担当区分:責任著者

     概要を見る

    Cereblon (CRBN) was identified as a gene that causes intellectual disabilities. The encoded CRBN protein, containing 442 amino acids, is located in several organs. Cytosolic CRBN was reported to mainly act as a component of the E3 ubiquitin ligase complex. CRBN is one of the substrate receptors of the E3 ubiquitin ligase complex and promotes the degradation of targeted proteins. Studies have reported that CRBN recognizes the C-terminal region of the amyloid precursor protein (APP), a protein known for its involvement in the development of Alzheimer's disease. Although CRBN may interact with the C-terminal region of APP in mice, the CRBN-mediated degradation mechanism of human APP remains unclear. Here, we analyzed the CRBN-mediated degradation mechanism of human APP via the ubiquitin-proteasome system. Immunoprecipitation experiments showed that CRBN interacts with human full-length APP via its C-terminal region. Next, we examined CRBN-mediated degradation of APP in the ubiquitin-proteasome system. CRBN recognizes Lys751 in human APP and ubiquitinates it in SH-SY5Y cells. Overexpression of CRBN decreased wild-type APP expression levels. In contrast, the expression level of K751R APP remained unchanged by CRBN overexpression, while knockdown of endogenous CRBN increased APP levels. As such, our results suggest that CRBN ubiquitinates Lys751 of human APP thereby degrading it via the ubiquitin-proteasome system.

    DOI PubMed

  • Light-driven activation of mitochondrial proton-motive force improves motor behaviors in a Drosophila model of Parkinson's disease.

    Imai Y, Inoshita T, Meng H, Shiba-Fukushima K, Hara KY, Sawamura N, Hattori N

    Communications biology   2   424  2019年12月  [査読有り]

    DOI PubMed

  • Mammalian cell cultivation using nutrients extracted from microalgae.

    Okamoto Y, Haraguchi Y, Sawamura N, Asahi T, Shimizu T

    Biotechnology progress   36 ( 2 ) e2941  2019年11月  [査読有り]

    DOI PubMed

  • Data for positive selection test and co-evolutionary analysis on mammalian cereblon

    Wataru Onodera, Toru Asahi, Naoya Sawamura

    Data in Brief   26  2019年10月  [査読有り]

    担当区分:責任著者

     概要を見る

    © 2019 The Author(s) Cereblon (CRBN) is a substrate recognition subunit of the CRL4 E3 ubiquitin ligase complex, directly binding to specific substrates for poly-ubiquitination followed by proteasome-dependent degradation of proteins. Cellular CRBN is responsible for energy metabolism, ion-channel activation, and cellular stress response through binding to proteins related to the respective pathways. As CRBN binds to various proteins, the selective pressure at the interacting surface is expected to result in functional divergence. Here, we present two mammalian CRBN datasets of molecular evolutionary analyses. (1) The multiple sequence alignment data shows that positive selection occurred, determined with a dN/dS calculation. (2) Data on co-evolutionary analysis between vertebrate CRBN and related proteins are represented by calculating the correlation coefficient based on the comparison of phylogenetic trees. Co-evolutionary analysis shows the similarity of evolutionary traits of two proteins. Further molecular, functional interpretation of these analyses is explained in ‘Positive selection of Cereblon modified function including its E3 Ubiquitin Ligase activity and binding efficiency with AMPK’ (W. Onodera, T. Asahi, N. Sawamura, Positive selection of cereblon modified function including its E3 ubiquitin ligase activity and binding efficiency with AMPK. Mol Phylogenet Evol. (2019) 135:78-85. [1]).

    DOI

  • サリドマイドによるAMPキナーゼを介した脳梗塞に対する神経保護効果 (特集 AMPキナーゼと医学)

    澤村 直哉, 朝日 透, 高木 教夫

    医学のあゆみ   269 ( 12 ) 915 - 919  2019年06月

    CiNii

  • Positive Selection of Cereblon Modified Function Including its E3 Ubiquitin Ligase Activity and Binding Efficiency with AMPK.

    Onodera W, Asahi T, Sawamura N

    Molecular phylogenetics and evolution    2019年03月  [査読有り]

    担当区分:責任著者

    DOI PubMed

  • The Neuroprotective Effect of Thalidomide against Ischemia through the Cereblon-mediated Repression of AMPK Activity

    Naoya Sawamura, Mariko Yamada, Miku Fujiwara, Haruka Yamada, Hideki Hayashi, Norio Takagi, Toru Asahi

    Scientific Reports   8 ( 1 )  2018年12月

     概要を見る

    Thalidomide was originally used as a sedative and found to be a teratogen, but now thalidomide and its derivatives are widely used to treat haematologic malignancies. Accumulated evidence suggests that thalidomide suppresses nerve cell death in neurologic model mice. However, detailed molecular mechanisms are unknown. Here we examined the molecular mechanism of thalidomide's neuroprotective effects, focusing on its target protein, cereblon (CRBN), and its binding protein, AMP-activated protein kinase (AMPK), which plays an important role in maintaining intracellular energy homeostasis in the brain. We used a cerebral ischemia rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). Thalidomide treatment significantly decreased the infarct volume and neurological deficits of MCAO/R rats. AMPK was the key signalling protein in this mechanism. Furthermore, we considered that the AMPK-CRBN interaction was altered when neuroprotective action by thalidomide occurred in cells under ischemic conditions. Binding was strong between AMPK and CRBN in normal SH-SY5Y cells, but was weakened by the addition of H2O2. However, when thalidomide was administered at the same time as H2O2, the binding of AMPK and CRBN was partly restored. These results suggest that thalidomide inhibits the activity of AMPK via CRBN under oxidative stress and suppresses nerve cell death.

    DOI PubMed

  • Cholinergic receptor, nicotinic, alpha 7 as a target molecule of Arctic mutant amyloid β.

    Sawamura N, Ju Y, Asahi T

    Neural regeneration research   13 ( 8 ) 1360 - 1361  2018年08月  [査読有り]

    DOI PubMed

  • Antioxidant activity of Ge-132, a synthetic organic germanium, on cultured mammalian cells

    Takeyoshi Wada, Takashi Hanyu, Kota Nozaki, Kosuke Kataoka, Tomoro Kawatani, Toru Asahi, Naoya Sawamura

    Biological and Pharmaceutical Bulletin   41 ( 5 ) 749 - 753  2018年  [査読有り]

     概要を見る

    Ge-132 is a synthetic organic germanium that is used as a dietary supplement. The antioxidant activity of Ge-132 on cultured mammalian cells was investigated in this study. First, Ge-132 cytotoxicity on mammalian cultured cells was determined by measuring lactate dehydrogenase (LDH) levels. Ge-132 had no cytotoxic effect on three different cell lines. Second, the cell proliferative effect of Ge-132 was determined by measuring ATP content of whole cells and counting them. Ge-132 treatment of Chinese hamster ovary (CHO-K1) and SH-SY5Y cells promoted cell proliferation in a dose-dependent manner. Finally, antioxidant activity of Ge-132 against hydrogen peroxide-induced oxidative stress was determined by measuring the levels of intracellular reactive oxygen species (ROS) and carbonylated proteins. Pre-incubation of CHO-K1 and SH-SY5Y cells with Ge-132 suppressed intracellular ROS production and carbonylated protein levels induced by hydrogen peroxide. Our results suggest that Ge-132 has antioxidant activity against hydrogen peroxide-induced oxidative stress.

    DOI PubMed

  • Arctic A beta 40 blocks the nicotine-induced neuroprotective effect of CHRNA7 by inhibiting the ERK1/2 pathway in human neuroblastoma cells

    Ye Ju, Toru Asahi, Naoya Sawamura

    NEUROCHEMISTRY INTERNATIONAL   110   49 - 56  2017年11月  [査読有り]

     概要を見る

    Amyloid 13 protein (A beta) plays a central role in Alzheimer's disease (AD) pathogenesis. Point mutations in the A beta sequence, which cluster around the central hydrophobic core of the peptide, are associated with familial AD (FAD). Several mutations have been identified, with the Arctic mutation exhibiting a purely cognitive phenotype that is typical of AD. Our previous findings suggest that Arctic A beta 40 binds to and aggregates with CHRNA7, thereby inhibiting the calcium response and signaling pathways downstream of the receptor. Activation of CHRNA7 is neuroprotective both in vitro and in vivo. Therefore, in the present study, we investigated whether Arctic A beta 40 affects neuronal survival and/or death via CHRNA7. Using human neuroblastoma SH-SY5Y cells, we found that the neuroprotective function of CHRNA7 is blocked by CHRNA7 knockdown using RNA interference. Furthermore, Arctic A beta 40 blocked the neuroprotective effect of nicotine by inhibiting the ERK1/2 pathway downstream of CHRNA7. Moreover, we show that ERK1/2 activation mediates the neuroprotective effect of nicotine against oxidative stress. Collectively, our findings further our understanding of the molecular pathogenesis of Arctic FAD. (C) 2017 Elsevier Ltd. All rights reserved.

    DOI

  • Arctic Aβ40 blocks the nicotine-induced neuroprotective effect of CHRNA7 by inhibiting the ERK1/2 pathway in human neuroblastoma cells.

    Ju Ye, Asahi Toru, Sawamura Naoya

    Neurochemistry international   110   49 - 56  2017年11月

     概要を見る

    :Amyloid β protein (Aβ) plays a central role in Alzheimer's disease (AD) pathogenesis. Point mutations in the Aβ sequence, which cluster around the central hydrophobic core of the peptide, are associated with familial AD (FAD). Several mutations have been identified, with the Arctic mutation exhibiting a purely cognitive phenotype that is typical of AD. Our previous findings suggest that Arctic Aβ40 binds to and aggregates with CHRNA7, thereby inhibiting the calcium response and signaling pathways downstream of the receptor. Activation of CHRNA7 is neuroprotective both in vitro and in vivo. Therefore, in the present study, we investigated whether Arctic Aβ40 affects neuronal survival and/or death via CHRNA7. Using human neuroblastoma SH-SY5Y cells, we found that the neuroprotective function of CHRNA7 is blocked by CHRNA7 knockdown using RNA interference. Furthermore, Arctic Aβ40 blocked the neuroprotective effect of nicotine by inhibiting the ERK1/2 pathway downstream of CHRNA7. Moreover, we show that ERK1/2 activation mediates the neuroprotective effect of nicotine against oxidative stress. Collectively, our findings further our understanding of the molecular pathogenesis

    DOI PubMed

  • Ohgata, the Single Drosophila Ortholog of Human Cereblon, Regulates Insulin Signaling-dependent Organismic Growth

    Satoru Wakabayashi, Naoya Sawamura, Andre Voelzmann, Meike Broemer, Toru Asahi, Michael Hoch

    JOURNAL OF BIOLOGICAL CHEMISTRY   291 ( 48 ) 25120 - 25132  2016年11月  [査読有り]

     概要を見る

    Cereblon (CRBN) is a substrate receptor of the E3 ubiquitin ligase complex that is highly conserved in animals and plants. CRBN proteins have been implicated in various biological processes such as development, metabolism, learning, and memory formation, and their impairment has been linked to autosomal recessive non-syndromic intellectual disability and cancer. Furthermore, human CRBN was identified as the primary target of thalidomide teratogenicity. Data on functional analysis of CRBN family members in vivo, however, are still scarce. Here we identify Ohgata (OHGT), the Drosophila ortholog of CRBN, as a regulator of insulin signaling-mediated growth. Using ohgt mutants that we generated by targeted mutagenesis, we show that its loss results in increased body weight and organ size without changes of the body proportions. We demonstrate that ohgt knockdown in the fat body, an organ analogous to mammalian liver and adipose tissue, phenocopies the growth phenotypes. We further show that overgrowth is due to an elevation of insulin signaling in ohgt mutants and to the down-regulation of inhibitory cofactors of circulating Drosophila insulin-like peptides (DILPs), named acid-labile subunit and imaginal morphogenesis protein-late 2. The two inhibitory proteins were previously shown to be components of a heterotrimeric complex with growth-promoting DILP2 and DILP5. Our study reveals OHGT as a novel regulator of insulin-dependent organismic growth in Drosophila.

    DOI PubMed

  • Nuclear cereblon modulates transcriptional activity of Ikaros and regulates its downstream target, enkephalin, in human neuroblastoma cells

    Takeyoshi Wada, Toru Asahi, Naoya Sawamura

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   477 ( 3 ) 388 - 394  2016年08月

     概要を見る

    The gene coding cereblon (CRBN) was originally identified in genetic linkage analysis of mild autosomal recessive nonsyndromic intellectual disability. CRBN has broad localization in both the cytoplasm and nucleus. However, the significance of nuclear CRBN remains unknown. In the present study, we aimed to elucidate the role of CRBN in the nucleus. First, we generated a series of CRBN deletion mutants and determined the regions responsible for the nuclear localization. Only CRBN protein lacking the N-terminal region was localized outside of the nucleus, suggesting that the N-terminal region is important for its nuclear localization. CRBN was also identified as a thalidomide-binding protein and component of the cullin-4-containing E3 ubiquitin ligase complex. Thalidomide has been reported to be involved in the regulation of the transcription factor Ikaros by CRBN-mediated degradation. To investigate the nuclear functions of CRBN, we performed co-immunoprecipitation experiments and evaluated the binding of CRBN to Ikaros. As a result, we found that CRBN was associated with Ikaros protein, and the N-terminal region of CRBN was required for Ikaros binding. In luciferase reporter gene experiments, CRBN modulated transcriptional activity of Ikaros. Furthermore, we found that CRBN modulated Ikaros-mediated transcriptional repression of the proenkephalin gene by binding to its promoter region. These results suggest that CRBN binds to Ikaros via its N-terminal region and regulates transcriptional activities of Ikaros and its downstream target, enkephalin. (C) 2016 Elsevier Inc. All rights reserved.

    DOI PubMed

  • Mitochondrial cereblon functions as a Lon-type protease

    Kosuke Kataoka, China Nakamura, Toru Asahi, Naoya Sawamura

    SCIENTIFIC REPORTS   6   29986  2016年07月  [査読有り]

     概要を見る

    Lon protease plays a major role in the protein quality control system in mammalian cell mitochondria. It is present in the mitochondrial matrix, and degrades oxidized and misfolded proteins, thereby protecting the cell from various extracellular stresses, including oxidative stress. The intellectual disability-associated and thalidomide-binding protein cereblon (CRBN) contains a large, highly conserved Lon domain. However, whether CRBN has Lon protease-like function remains unknown. Here, we determined if CRBN has a protective function against oxidative stress, similar to Lon protease. We report that CRBN partially distributes in mitochondria, suggesting it has a mitochondrial function. To specify the mitochondrial role of CRBN, we mitochondrially expressed CRBN in human neuroblastoma SH-SY5Y cells. The resulting stable SH-SY5Y cell line showed no apparent effect on the mitochondrial functions of fusion, fission, and membrane potential. However, mitochondrially expressed CRBN exhibited protease activity, and was induced by oxidative stress. In addition, stably expressed cells exhibited suppressed neuronal cell death induced by hydrogen peroxide. These results suggest that CRBN functions specifically as a Lon-type protease in mitochondria.

    DOI PubMed

  • Cereblon is recruited to aggresome and shows cytoprotective effect against ubiquitin-proteasome system dysfunction

    Naoya Sawamura, Satoru Wakabayashi, Kodai Matsumoto, Haruka Yamada, Toru Asahi

    Biochemical and Biophysical Research Communications   464 ( 4 ) 1054 - 1059  2015年09月

     概要を見る

    Cereblon (CRBN) is encoded by a candidate gene for autosomal recessive nonsyndromic intellectual disability (ID). The nonsense mutation, R419X, causes deletion of 24 amino acids at the C-terminus of CRBN, leading to mild ID. Although abnormal CRBN function may be associated with ID disease onset, its cellular mechanism is still unclear. Here, we examine the role of CRBN in aggresome formation and cytoprotection. In the presence of a proteasome inhibitor, exogenous CRBN formed perinuclear inclusions and co-localized with aggresome markers. Endogenous CRBN also formed perinuclear inclusions under the same condition. Treatment with a microtubule destabilizer or an inhibitor of the E3 ubiquitin ligase activity of CRBN blocked formation of CRBN inclusions. Biochemical analysis showed CRBN containing inclusions were high-molecular weight, ubiquitin-positive. CRBN overexpression in cultured cells suppressed cell death induced by proteasome inhibitor. Furthermore, knockdown of endogenous CRBN in cultured cells increased cell death induced by proteasome inhibitor, compared with control cells. Our results show CRBN is recruited to aggresome and has functional roles in cytoprotection against ubiquitin-proteasome system impaired condition.

    DOI PubMed

  • Cereblon is recruited to aggresome and shows cytoprotective effect against ubiquitin-proteasome system dysfunction

    Naoya Sawamura, Satoru Wakabayashi, Kodai Matsumoto, Haruka Yamada, Toru Asahi

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   464 ( 4 ) 1054 - 1059  2015年09月  [査読有り]

     概要を見る

    Cereblon (CRBN) is encoded by a candidate gene for autosomal recessive nonsyndromic intellectual disability (ID). The nonsense mutation, R419X, causes deletion of 24 amino acids at the C-terminus of CRBN, leading to mild ID. Although abnormal CRBN function may be associated with ID disease onset, its cellular mechanism is still unclear. Here, we examine the role of CRBN in aggresome formation and cytoprotection. In the presence of a proteasome inhibitor, exogenous CRBN formed perinuclear inclusions and co-localized with aggresome markers. Endogenous CRBN also formed perinuclear inclusions under the same condition. Treatment with a microtubule destabilizer or an inhibitor of the E3 ubiquitin ligase activity of CRBN blocked formation of CRBN inclusions. Biochemical analysis showed CRBN containing inclusions were high-molecular weight, ubiquitin-positive. CRBN overexpression in cultured cells suppressed cell death induced by proteasome inhibitor. Furthermore, knockdown of endogenous CRBN in cultured cells increased cell death induced by proteasome inhibitor, compared with control cells. Our results show CRBN is recruited to aggresome and has functional roles in cytoprotection against ubiquitin-proteasome system impaired condition. (C) 2015 Elsevier Inc. All rights reserved.

    DOI

  • Arctic mutant Aß40 aggregates on α7 nicotinic acetylcholine receptors and inhibits their functions

    Ye Ju, Toru Asahi, Naoya Sawamura

    Journal of Neurochemistry   131 ( 5 ) 667 - 674  2014年12月

     概要を見る

    :Amyloid β protein (Aβ) plays a central role in the pathogenesis of Alzheimer's disease (AD). Point mutations within the Aβ sequence associated with familial AD (FAD) are clustered around the central hydrophobic core of Aβ. Several types of mutations within the Aβ sequence have been identified, and the 'Arctic' mutation (E22G) has a purely cognitive phenotype typical of AD. Previous studies have shown that the primary result of the 'Arctic' mutation is increased formation of Aβ protofibrils. However, the molecular mechanism underlying this effect remains unknown. Aβ42 binds to a neuronal nicotinic acetylcholine receptor subunit, neuronal acetylcholine receptor subunit alpha-7 (CHRNA7), with high affinity and, thus, may be involved in the pathogenesis of AD. Therefore, to clarify the molecular mechanism of Arctic mutation-mediated FAD, we focused on CHRNA7 as a target molecule of Arctic Aβ. We performed an in vitro binding assay using purified CHRNA7 and synthetic Arctic Aβ40, and demonstrated that Arctic Aβ40 specifically bound to CHRNA7. The aggregation of Arctic Aβ40 was enhanced with the addition of CHRNA7. Furthermore, the function of CHRNA7 was detected by measuring

    DOI PubMed

  • A label-free electrical assay of fibrous amyloid β based on semiconductor biosensing.

    Hideshima, S, Kobayashi, M, Wada, T, Kuroiwa, S, Nakanishi, T, Sawamura, N, Asahi T, Osaka, T

    Chemical Communications   50 ( 26 ) 3476 - 3479  2014年

    DOI

  • Construction of photoenergetic mitochondria in cultured mammalian cells

    Kiyotaka Y. Hara, Takeyoshi Wada, Kuniki Kino, Toru Asahi, Naoya Sawamura

    Scientific Reports   3   1635  2013年04月

     概要を見る

    The proton motive force (PMF) is bio-energetically important for various cellular reactions to occur. We developed PMF-photogenerating mitochondria in cultured mammalian cells. An archaebacterial rhodopsin, delta-rhodopsin, which is a light-driven proton pump derived from Haloterrigena turkmenica, was expressed in the mitochondria of CHO-K1 cells. The constructed stable CHO-K1 cell lines showed suppression of cell death induced by rotenone, a pesticide that inhibits mitochondrial complex I activity involved in PMF generation through the electron transport chain. Delta-rhodopsin was also introduced into the mitochondria of human neuroblastoma SH-SY5Y cells. The constructed stable SH-SY5Y cell lines showed suppression of dopaminergic neuronal cell death induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), an inducer of Parkinson's disease models, which acts through inhibition of complex I activity. These results suggest that the light-activated proton pump functioned as a PMF generator in the mitochondria of mammalian cells, and suppressed cell death induced by inhibition of respiratory PMF generation.

    DOI PubMed

  • Construction of new energy synthesis system in SH-SY5Y cells: application for the treatment of Parkinson's disease.

    T. Wada, K. Hara, Y. Asahi, N. Sawamura

    JOURNAL OF NEUROCHEMISTRY   123   24 - 25  2012年10月

  • Cereblon accumulates in aggresomes due to proteasome impairment

    S. Wakabayashi, H. Yamada, T. Asahi, N. Sawamura

    JOURNAL OF NEUROCHEMISTRY   123   25 - 25  2012年10月

  • Nuclear DISC1 regulates CRE-mediated gene transcription and sleep homeostasis in the fruit fly

    N. Sawamura, T. Ando, Y. Maruyama, M. Fujimuro, H. Mochizuki, K. Honjo, M. Shimoda, H. Toda, T. Sawamura-Yamamoto, L. A. Makuch, A. Hayashi, K. Ishizuka, N. G. Cascella, A. Kamiya, N. Ishida, T. Tomoda, T. Hai, K. Furukubo-Tokunaga, A. Sawa

    MOLECULAR PSYCHIATRY   13 ( 12 ) 1138 - 1148  2008年12月

     概要を見る

    Disrupted-in-schizophrenia-1 (DISC1) is one of major susceptibility factors for a wide range of mental illnesses, including schizophrenia, bipolar disorder, major depression and autism spectrum conditions. DISC1 is located in several subcellular domains, such as the centrosome and the nucleus, and interacts with various proteins, including NudE-like (NUDEL/NDEL1) and activating transcription factor 4 (ATF4)/CREB2. Nevertheless, a role for DISC1 in vivo remains to be elucidated. Therefore, we have generated a Drosophila model for examining normal functions of DISC1 in living organisms. DISC1 transgenic flies with preferential accumulation of exogenous human DISC1 in the nucleus display disturbance in sleep homeostasis, which has been reportedly associated with CREB signaling/CRE-mediated gene transcription. Thus, in mammalian cells, we characterized nuclear DISC1, and identified a subset of nuclear DISC1 that colocalizes with the promyelocytic leukemia (PML) bodies, a nuclear compartment for gene transcription. Furthermore, we identified three functional cis-elements that regulate the nuclear localization of DISC1. We also report that DISC1 interacts with ATF4/CREB2 and a corepressor N-CoR, modulating CRE-mediated gene transcription.

    DOI

  • The fruitfly Drosophila melanogaster: A promising model to explore molecular psychiatry

    N. Sawamura, N. Ishida, T. Tomoda, T. Hai, K. Furukubo-Tokunaga, A. Sawa

    Molecular Psychiatry   13 ( 12 ) 1069 - 1069  2008年12月

    DOI

  • Molecules regulated by patterns of electrical activity

    Miwako Ozaki, Naoya Sawamura, Michinori Ichikawa

    NEUROSCIENCE RESEARCH   58   S142 - S142  2007年

  • Primate disrupted-in-schizophrenia-1 (DISC1): High divergence of a gene for major mental illnesses in recent evolutionary history

    Lyuda Bord, Jeff Wheeler, Matthew Paek, Masoumeh Saleh, Ariel Lyons-Warren, Christopher A. Ross, Naoya Sawamura, Akira Sawa

    NEUROSCIENCE RESEARCH   56 ( 3 ) 286 - 293  2006年11月

     概要を見る

    Here we analyze the species conservation of disrupted-in-schizophrenia-1 (DISC1) gene, a susceptibility gene for schizophrenia. We cloned cDNA of DISCI and characterized DISCI protein in monkey brains and compared their features with those in a variety of species, including humans, rodents and lower vertebrates. Sequences of human and monkey DISCI are very similar for both nucleotides and amino acids, in sharp contrast to those of rodents; this is reminiscent of G72, another gene involved in major mental illnesses. Bioinformatic cross-species comparisons identified a portion of DISC] sequences in chicken and Caenorhabditis elegans, but failed to find DISC1 in Drosophila. In contrast to sequence differences, the regional expression profile of DISCI is well conserved between rodents and primates in that levels of DISC I mRNA and protein are higher in the hippocampus and the cerebral cortex, and much lower in cerebellum in adult brains. The findings of this study may suggest overall patterns of evolution of genes for psychiatric disorders, and thus assist in production of genetically-engineered mice, and the interpretation of the underlying mechanisms of psychiatric conditions. Published by Elsevier Ireland Ltd on behalf of Japan Neuroscience Society.

    DOI

  • Disrupted-in-Schizophrenia-1 (DISC1) - A key susceptibility factor for major mental illnesses

    Naoya Sawamura, Akira Sawa

    INTEGRATED MOLECULAR MEDICINE FOR NEURONAL AND NEOPLASTIC DISORDERS   1086   126 - 133  2006年

     概要を見る

    Here we overview Disrupted-in-Schizophrenia-1 (DISC1), a promising lead in studying the pathophysiology of major mental conditions. Genetic association studies reproducibly suggest involvement of DISC1 in both schizophrenia and bipolar disorder in several ethnic groups. Different from several other susceptibility genes for schizophrenia, such as neuregulin-1 and dysbindin, there are two independent pedigrees in which genetic variations of DISC1 directly segregate with major mental conditions. This uniqueness has facilitated neurobiology of DISC1, which may hopefully lead to an important breakthrough in understanding of pathophysiology of major mental conditions. DISC1 is a multifunctional protein that plays a role in neurodevelopment and cell signaling. In autopsied brains from patients with psychosis and substance abuse, change in subcellular distribution of DISC1 is observed. DISC1 interacts with phosphodiesterase (PDE) 4B that degrades cyclic AMP (cAMP), which may be a regulatory molecule for working memory in the prefrontal cortex. Knockdown expression of DISC1 in developing cerebral cortex in mouse brains leads to changes that resemble, at least in part, the pathology found in patients with schizophrenia. These results support involvement of DISC1 in the pathophysiology of major mental conditions, including schizophrenia, in several mechanisms.

    DOI

  • 【統合失調症の分子医学】 DISC1からみた統合失調症の分子病態

    疋田 貴俊, 澤村 直哉, 尾関 祐二, 神谷 篤, 澤 明

    細胞   37 ( 14 ) 573 - 576  2005年12月

     概要を見る

    統合失調症の病態に複数の遺伝子と環境要因の関与が指摘されている.最近連鎖研究・関連研究からいくつかの統合失調症の候補遺伝子が明らかになってきた.本稿では,そのなかからDISC1(Disrupted-In-Schizophrenia 1)からみた統合失調症の病態研究を展望する.DISC1は精神疾患多発単一家系から発見されたが,遺伝学的研究と統合失調症患者剖検脳を用いた生化学的研究から統合失調症一般例においてもDISC1の統合失調症への関与が示唆されている.DISC1は多くの細胞内部位で働く多機能タンパクであり,特に細胞骨格に関与して神経発達に重要な役割を果たしている.DISC1のさらなる解析,特にDISC1のトランスジェニックマウスによる統合失調症の動物モデルの確立が統合失調症の病態理解や治療法の開発につながることが期待される(著者抄録)

  • A schizophrenia-associated mutation of DISC1 perturbs cerebral cortex development

    A Kamiya, K Kubo, T Tomoda, M Takaki, R Youn, Y Ozeki, N Sawamura, U Park, C Kudo, M Okawa, CA Ross, ME Hatten, K Nakajima, A Sawa

    NATURE CELL BIOLOGY   7 ( 12 ) 1167 - 1178  2005年12月

     概要を見る

    Disrupted-In-Schizophrenia-1 (DISC1), originally identified at the breakpoint of a chromosomal translocation that is linked to a rare familial schizophrenia, has been genetically implicated in schizophrenia in other populations. Schizophrenia involves subtle cytoarchitectural abnormalities that arise during neurodevelopment, but the underlying molecular mechanisms are unclear. Here, we demonstrate that DISC1 is a component of the microtubule-associated dynein motor complex and is essential for maintaining the complex at the centrosome, hence contributing to normal microtubular dynamics. Carboxy-terminal-truncated mutant DISC1 (mutDISC1), which results from a chromosomal translocation, functions in a dominant-negative manner by redistributing wildtype DISC1 through self-association and by dissociating the DISC1-dynein complex from the centrosome. Consequently, either depletion of endogenous DISC1 or expression of mutDISC1 impairs neurite outgrowth in vitro and proper development of the cerebral cortex in vivo. These results indicate that DISC1 is involved in cerebral cortex development, and suggest that loss of DISCI function may underlie neurodevelopmental dysfunction in schizophrenia.

    DOI

  • DISC1からみた統合失調症の分子病態 (特集 統合失調症の分子医学)

    疋田 貴俊, 澤村 直哉, 尾関 祐二

    細胞   37 ( 14 ) 573 - 576  2005年12月

  • Disrupted-In-Schizophrenia-1 (DISC1): A promising lead in molecular analyzes of schizophrenia

    A Sawa, N Sawamura, R Balkissoon

    CLINICAL NEUROSCIENCE RESEARCH   5 ( 1 ) 23 - 30  2005年09月

     概要を見る

    Although the genetics of schizophrenia (SZ) remains unresolved, recently both linkage/association studies and cytogenetic approaches have clarified several possible genes for SZ. In the neuropathology of SZ, many now agree that there are at least cytoarchitectural abnormalities such as alterations in synaptic, dendritic, and axonal organization, but clear molecular markers unique to SZ are still missing.
    In this review, we propose an approach relying on Disrupted-In-Schizophrenia-1 (DISC1), a candidate gene for SZ that may shed light on the molecular neuropathology of SZ. DISC1 was originally identified as the sole disrupted gene with an open reading frame, from a 'unique' Scottish family in which familial SZ and other major mental illnesses occur in tight association with a hereditary chromosomal abnormality. Additional genetic and biochemical approaches using autopsied brains from patients with SZ from other populations than the Scottish family suggest that DISC1 may be implicated not only in the Scottish family but also in general' cases of SZ. Furthermore. functional dissection of DISC1 protein indicates that DISC1 is a cytoskeletal protein that plays a key role in neurodevelopment, which may be relevant to the pathogenesis of SZ.
    Here, we provide a summary of the current updates of studies of DISC1 and their future perspective, especially its possible role in the pathophysiology of SZ, in association with other genetic and environmental factors. (c) 2005 Association for Research in Nervous and Mental Disease. Published by Elsevier B.V. All rights reserved.

    DOI

  • Production of DISC1 transgenic and knockout mice

    T Hikida, N Sawamura, M Paek, M Cascio, A Sawa

    AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS   138B ( 1 ) 134 - 135  2005年09月

  • A form of DISC1 enriched in nucleus: Altered subcellular distribution in orbitofrontal cortex in psychosis and substance/alcohol abuse

    N Sawamura, T Sawamura-Yamamoto, Y Ozeki, CA Ross, A Sawa

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   102 ( 4 ) 1187 - 1192  2005年01月  [査読有り]

     概要を見る

    Disrupted-In-Schizophrenia 1 (DISC1) was identified as the sole gene whose ORF is truncated and cosegregates with major mental illnesses in a Scottish family. DISC1 has also been suggested, by association and linkage studies, to be a susceptibility gene for schizophrenia (SZ) in independent populations. However, no analysis of DISC1 protein in human brains, especially those of patients with SZ, has yet been conducted. Here we performed a biochemical analysis of DISC1 protein in a well characterized set of autopsied brains, including brains of patients with SZ, bipolar disorder, and major depression (MD), as well as normal control brains. We identified an isoform of DISC1 by using MS and demonstrated that it is enriched in the nucleus of HeLa cells. In the orbitofrontal cortex, the subcellular distribution of this DISC1 isoform, assessed by the nuclear to cytoplasmic ratio in the immunoreactivity of the isoform, is significantly changed in brains from patients with SZ and MD. This altered distribution is also observed in those subjects with substance and alcohol abuse. The changes in MD brains are significantly influenced by substance/alcohol abuse as well as postmortem interval; however, the alteration in SZ brains is free from brain-associated confounding factors, although an interaction with substance/alcohol abuse cannot be completely ruled out. These results suggest that DISC1 may be implicated in psychiatric conditions in other populations than the unique Scottish family.

    DOI PubMed

  • A form of Disrupted-In-Schizophrenia-1 (DISC1) enriched in the nucleus has altered subcellular distribution in schizophrenia brains.

    Sawamura N, Sawamura-Yamamoto T, Ozeki Y, Ross C.A, Sawa A

    Proceedings of the National Academy of Sciences   102   1187 - 1192  2005年

  • Modulation of amyloid precursor protein cleavage by cellular sphingolipids

    N Sawamura, MH Ko, WX Yu, K Zou, K Hanada, T Suzuki, JS Gong, K Yanagisawa, M Michikawa

    JOURNAL OF BIOLOGICAL CHEMISTRY   279 ( 12 ) 11984 - 11991  2004年03月

     概要を見る

    Lipid rafts and their component, cholesterol, modulate the processing of beta-amyloid precursor protein (APP). However, the role of sphingolipids, another major component of lipid rafts, in APP processing remains undetermined. Here we report the effect of sphingolipid deficiency on APP processing in Chinese hamster ovary cells treated with a specific inhibitor of serine palmitoyltransferase, which catalyzes the first step of sphingolipid biosynthesis, and in a mutant LY-B strain defective in the LCB1 subunit of serine palmitoyltransferase. We found that in sphingolipid-deficient cells, the secretion of soluble APPalpha (sAPPalpha) and the generation of C-terminal fragment cleaved at alpha-site dramatically increased, whereas epsilon-cleavage activity remained unchanged, and the epsilon-cleavage activity decreased without alteration of the total APP level. The secretion of amyloid beta-protein 42 increased in sphingolipid-deficient cells, whereas that of amyloid beta-protein 40 did not. All of these alterations were restored in sphingolipid-deficient cells by adding exogenous sphingosine and in LY-B cells by transfection with cLCB1. Sphingolipid deficiency increased MAPK/ERK activity and a specific inhibitor of MAPK kinase, PD98059, restored sAPPalpha level, indicating that sphingolipid deficiency enhances sAPPalpha secretion via activation of MAPK/ERK pathway. These results suggest that not only the cellular level of cholesterol but also that of sphingolipids may be involved in the pathological process of Alzheimer's disease by modulating APP cleavage.

    DOI

  • 【脳・神経研究2004 神経発生・可塑性と高次脳機能のメカニズム,そして脳・神経疾患の分子機構の解明へ】 脳神経機能障害・疾患研究 統合失調症とDISC1

    澤村 直哉, 澤 明

    実験医学   21 ( 17 ) 2469 - 2473  2003年11月

     概要を見る

    統合失調症は思春期に好発する難治性の精神疾患である.その有病率は人口の1%に及び,継続的な医療が必要にも拘わらず,社会復帰や根治が困難であることから,その病態の把握は急務となっている.こうした中,遺伝学的検索から発見されたDisrupted-In-Schizophrenia 1(DISC1)は,精神疾患研究でおそらく最初にみとめられた候補遺伝子であり,このDISC1及びその遺伝子産物の解析を進めることにより,その病態に迫ることができるのではないかと現在期待されている

  • Amyloid beta-protein (Aß)1-40 protects neurons from damage induced by Aß1-42 in culture and in rat brain

    Zou K, Kim D, Kakio A, Byun K, Gong J.S, Kim J, Kim M, Sawamura N, Nishimoto S, Matsuzaki K, Lee B, Yanagisawa K, Michikawa M

    Journal of Neurochemistry   87 ( 3 ) 609 - 619  2003年11月

    DOI

  • Promotion of tau phosphorylation by MAP kinase Erk1/2 is accompanied by reduced cholesterol level in detergent-insoluble membrane fraction in Niemann-Pick C1-deficient cells

    N Sawamura, JS Gong, TY Chang, K Yanagisawa, M Michikawa

    JOURNAL OF NEUROCHEMISTRY   84 ( 5 ) 1086 - 1096  2003年03月

     概要を見る

    Niemann-Pick type C (NPC) disease is a cholesterol-storage disease accompanied by neurodegeneration with the formation of neurofibrillary tangles, the major component of which is the hyperphosphorylated tau. Here, we examined the mechanism underlying hyperphosphorylation of tau using mutant Chinese hamster ovary (CHO) cell line defective in NPC1 (CT43) as a tool. Immunoblot analysis revealed that tau was hyperphosphorylated at multiple sites in CT43 cells, but not in their parental cells (25RA) or the wild-type CHO cells. In CT43 cells, mitogen-activated protein (MAP) kinase Erk1/2 was activated and the specific MAPK inhibitor, PD98059, attenuated the hyperphosphorylation of tau. The amount of protein phosphatase 2A not bound to microtubules was decreased in CT43 cells. CT43 cells but not 25RA cells were amphotericin B-resistant, indicating that cholesterol level in the plasma membrane of CT43 is decreased. In addition, the level of cholesterol in the detergent-insoluble, low-density membrane (LDM) fraction of CT43 cells was markedly reduced compared with the other two types of CHO cells. As LDM domain plays critical role in signaling pathways, these results suggest that the reduced cholesterol level in LDM domain due to the lack of NPC1 may activate MAPK, which subsequently promotes tau phosphorylation in NPC1-deficient cells.

    DOI

  • 統合失調症とDISC1

    澤村 直哉, 澤 明

    実験医学 −脳・神経研究2004, 増刊−   21   2469 - 2473  2003年

  • Amyloid ß-protein affects cholesterol metabolism in cultured neurons: Implications for pivotal role of choleterol in the amyloid cascade.

    Gong J.S, Sawamura N, Zou K, Sakai J, Yanagisawa K, Michikawa M

    Neuroscience Research   70 ( 3 ) 438 - 446  2002年11月

    DOI

  • Apolipoprotein E (ApoE) isoform-dependent lipid release from astrocytes prepared from human ApoE3 and ApoE4 knock-in mice

    JS Gong, M Kobayashi, H Hayashi, K Zou, N Sawamura, SC Fujita, K Yanagisawa, M Michikawa

    JOURNAL OF BIOLOGICAL CHEMISTRY   277 ( 33 ) 29919 - 29926  2002年08月

     概要を見る

    We have reported previously (Michikawa, M., Fan, Q.-W., Isobe, I., and Yanagisawa, K. (2000) J. Neurochem. 74, 1008-1016) that exogenously added recombinant human apolipoprotein E (apoE) promotes cholesterol release in an isoform-dependent manner. However, the molecular mechanism underlying this isoform-dependent promotion of cholesterol release remains undetermined. In this study, we demonstrate that the cholesterol release is mediated by endogenously synthesized and secreted apoE isoforms and clarify the mechanism underlying this apoE isoform-dependent cholesterol release using cultured astrocytes prepared from human apoE3 and apoE4 knock-in mice. Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. The amount of cholesterol released into the culture media from the apoE3-expressing astrocytes was similar to2.5-fold greater than that from apoE4-expressing astrocytes. In contrast, the amount of apoE3 released in association with the HDL-like particles was similar to that of apoE4, and the sizes of the HDL-like particles released from apoE3- and apoE4-expressing astrocytes were similar. The molar ratios of cholesterol to apoE in the HDL fraction of the culture media of apoE3- and apoE4-expressing astrocytes were 250 +/- 6.0 and 119 +/- 5.1, respectively. These data indicate that apoE3 has an ability to generate similarly sized lipid particles with less number of apoE molecules, than apoE4, suggesting that apoE3-expressing astrocytes can supply more cholesterol to neurons than apoE4-expressing astrocytes. These findings provide a new insight into the issue concerning the putative alteration of apoE-related cholesterol metabolism in Alzheimer's disease.

    DOI

  • Cholesterol-dependent modulation of dendrite outgrowth and microtubule stability in cultured neurons (vol 80, pg 178, 2002)

    QW Fan, W Yu, JS Gong, K Zou, N Sawamura, T Senda, K Yanagisawa, M Michikawa

    JOURNAL OF NEUROCHEMISTRY   80 ( 5 ) 940 - 940  2002年03月

    DOI

  • A novel action of alzheimer's amyloid beta-protein (Aß): oligomeric Aß promotes lipid release

    Michikawa M, Gong J.S, Fan Q.W, Sawamura N, Yanagisawa K

    Journal of Neuroscience   21 ( 18 ) 7226 - 7235  2001年09月

  • Site-specific phosphorylation of tau accompanied by activation of mitogen-activated protein kinase (MAPK) in brains of Niemann-Pick type C mice

    N Sawamura, JS Gong, WS Garver, RA Heidenreich, H Ninomiya, K Ohno, K Yanagisawa, M Michikawa

    JOURNAL OF BIOLOGICAL CHEMISTRY   276 ( 13 ) 10314 - 10319  2001年03月

     概要を見る

    Niemann-Pick type C (NPC) disease is characterized by an accumulation of cholesterol in most tissues and progressive neurodegeneration with the formation of neurofibrillary tangles. Neurofibrillary tangles are composed of paired helical filaments (PHF), a major component of which is the hyperphosphorylated tau. In this study we used NPC heterozygous and NPC homozygous mouse brains to investigate the molecular mechanism responsible for tauopathy in NPC, Immunoblot analysis using anti-tau antibodies (Tau-1, PHF-1, AT-180, and AT-100) revealed site-specific phosphorylation of tau at Ser-396 and Ser-404 in the brains of NPC homozygous mice. Mitogen-activated protein kinase, a potential serine kinase known to phosphorylate tau, was activated, whereas other serine kinases such as glycogen synthase kinase-3 beta and cyclin-dependent kinase 5 were inactive. Morphological examination demonstrated that a number of neurons the perikarya of which strongly immunostained with PHF-1, exhibited polymorphorous cytoplasmic inclusion bodies and multi-concentric lamellar-like bodies. Importantly, the accumulation of intracellular cholesterol in NPC mouse brains was determined to be a function of age. From these results we conclude that abnormal cholesterol metabolism due to the genetic mutation in NPC1 may be responsible for activation of the mitogen-activated protein kinase-signaling pathway and site-specific phosphorylation of tau in vivo, leading to tauopathy in NPC.

    DOI

  • Mutant presenilin 2 transgenic mice: A large increase in the levels of Aß42 is presumably associated with the low density membrane domain that contains decreased levels of glycerophospholipids and sphingomyelin

    Sawamura N, Morishima-Kawashima M, Waki H, Kobayashi K, Kuramochi T, Frosch M.P, Ding K, Ito M, Kim T.W, Tanzi R.E, Oyama F, Tabira T, Ando S, Ihara Y

    Journal of Biological Chemistry   275 ( 36 ) 27901 - 27908  2000年09月

    DOI

  • Mutant presenilin 2 transgenic mouse: Effect on an age-dependent increase of amyloid ß-protein (Aß) 42 in the brain

    Sawamura N, Oyama F, Kobayashi K, Morishima-Kawashima M, Kuramochi T, Ito M, Tomita T, Maruyama K, Saido T.C, Iwatsubo T, Capell A, Walter J, Grunberg J, Ueyama Y, Haass C, Ihara Y, The, first, three authors contributed equally to this study

    Journal of Neurochemistry   71 ( 1 ) 313 - 322  1998年07月

    DOI

  • Deposition of amyloid ß protein (Aß) subtypes [Aß40 and Aß42(43)] in canine senile plaques and cerebral amyloid angiopathy

    Nakamura S, Tamaoka A, Sawamura N, Kiatipattanasakul W, Nakayama H, Shoji S, Yoshikawa Y, Doi K

    Acta Neuropathol (Berl)   94 ( 4 ) 323 - 328  1997年10月

    DOI

  • Characterization of amyloid ß protein species in cerebral amyloid angiopathy of a cynomolgous monkey by immunocytochemistry and enzyme-linked immunosorbent assay

    Sawamura N, Tamaoka A, Shoji S, Koo E.H, Walker L.C, Mori H

    Brain Research   764 ( 1-2 ) 225 - 229  1997年08月

    DOI

  • Amyloid ß protein 42(43) in cerebrospinal fluid of patients with Alzheimer's disease

    Tamaoka A, Sawamura N, Fukushima T, Shoji S, Matsubara E, Shoji M, Hirai S, Furiya Y, Endoh R, Mori H

    Journal of Neurological Sciences   148 ( 1 ) 41 - 45  1997年05月

    DOI

  • Amyloid ß protein in plasma from patients with sporadic Alzheimer's disease

    Tamaoka A, Fukushima T, Sawamura N, Ishikawa K, Oguni E, Komatsuzaki Y, Shoji S

    Journal of the Neurological Sciences   141 ( 1-2 ) 65 - 68  1996年09月

    DOI

  • Carboxyl end-specific monoclonal antibodies to Amyloid ß protein (Aß) subtypes (Aß40 and Aß42(43)) differentiate Aß in senile plaques and amyloid angiopathy in brains of aged cynomolgus monkeys

    Nakamura S, Tamaoka A, Sawamura N, Shoji S, Nakayama H, Ono F, Sakakibara I, Yoshikawa Y, Mori H, Goto N, Doi K

    Neuroscience Letters   201 ( 2 ) 151 - 154  1995年12月

    DOI

  • Amyloid ß protein 1-42/43 (Aß1-42/43) in cerebellar diffuse plaques: enzyme-linked immunosorbent assay and immunocytochemical study

    Tamaoka A, Sawamura N, Odaka A, Suzuki N, Mizusawa H, Shoji S, Mori H

    Brain Research   679 ( 1 ) 151 - 156  1995年05月

    DOI

  • Biochemical evidence for the long-tail form (Aß1-42/43) of amyloid ß protein as a seed molecule in cerebral deposits of Alzheimer's disease

    Tamaoka A, Kondo T, Odaka A, Sahara N, Sawamura N, Ozawa K, Suzuki N, Shoji S, Mori H

    Biochemical and Biophysical Research Communications   205 ( 1 ) 834 - 842  1994年11月

    DOI

▼全件表示

書籍等出版物

  • 生命科学概論 第2版

    澤村 直哉

    2019年03月

  • 生命科学概論

    澤村直哉, 朝日透 他

    朝倉書店  2012年04月

  • KEYWORD 精神第4版

    澤村 直哉, 尾崎美和子

    先端医学社  2007年

Misc

  • 微小管結合タンパク質タウの分子進化解析

    高田海冴, 小野寺航, 朝日透, 朝日透, 澤村直哉, 澤村直哉

    日本進化学会大会プログラム・講演要旨集(Web)   23rd  2021年

    J-GLOBAL

  • 遠縁な種に対して有効な焼きなまし法による分子系統樹構築法の提案

    小野寺航, 朝日透, 朝日透, 澤村直哉, 澤村直哉

    日本進化学会大会プログラム・講演要旨集(Web)   23rd  2021年

    J-GLOBAL

  • 遠縁な配列間に対して焼きなまし法による分子系統樹の構築は有効である

    小野寺航, 朝日透, 朝日透, 澤村直哉, 澤村直哉

    日本分子生物学会年会プログラム・要旨集(Web)   44th  2021年

    J-GLOBAL

  • E3ユビキチンリガーゼCereblonは小胞体ストレス誘導性の異常なグリコーゲン集積を制御する

    川崎晃太郎, 飯田万由花, 川井聡子, 小野寺航, 朝日透, 朝日透, 澤村直哉, 澤村直哉

    日本分子生物学会年会プログラム・要旨集(Web)   44th  2021年

    J-GLOBAL

  • 哺乳類APLP1のシナプス接着因子としての進化可能性

    小野寺航, 朝日透, 朝日透, 澤村直哉

    日本分子生物学会年会プログラム・要旨集(Web)   42nd  2019年

    J-GLOBAL

  • APPファミリーの分子進化解析により明らかになったAPLP1の神経系に特殊化した進化

    小野寺航, 朝日透, 朝日透, 澤村直哉

    日本進化学会大会プログラム・講演要旨集(Web)   21st  2019年

    J-GLOBAL

  • 電界効果トランジスタを用いた凝集形態の異なるアミロイドβの検出

    小林万純, 秀島翔, 黒岩繁樹, 中西卓也, 澤村直哉, 朝日透, 朝日透, 逢坂哲彌, 逢坂哲彌

    Chemical Sensors   29 ( Supplement A )  2013年

    J-GLOBAL

  • 電界効果トランジスタを用いた凝集形態の異なるアミロイドβの検出

    小林万純, 秀島翔, 黒岩繁樹, 中西卓也, 澤村直哉, 朝日透, 逢坂哲彌, 朝日透, 逢坂哲彌

    電気化学会大会講演要旨集   80th  2013年

    J-GLOBAL

  • ニューレグリンの切断機構に着目した統合失調症発症の分子メカニズムの解明

    澤村直哉

    上原記念生命科学財団研究報告集(CD-ROM)   22   ROMBUNNO.101 - 4  2008年12月

     概要を見る

    膜貫通型タンパク質であるニューレグリン(NRG)1の切断異常により、統合失調症をはじめとする精神神経疾患発症に至るという仮説のもとに、分子生物学生化学的手法によりNRG1の切断機構を解明することにより、統合失調症をはじめとする精神神経疾患の創薬ターゲットの同定を目指して研究した。NRG1の断片を認識する抗体を用いて免疫沈降法を行い、NRG断片の濃縮精製を試みた。NRG1を発現した大量の細胞のライセートに抗体とプロテインAセファロースを混ぜて反応させた。熱処理によりサンプルを回収し、電気泳動を行い、ゲルから目的の断片を回収した。NRG1タンパクの断片を抗NRG1抗体による免疫沈降法により精製することに成功した。

    J-GLOBAL

  • スフィンゴ脂質によるアミロイド前駆体蛋白の代謝制御

    澤村 直哉, 高 美姫, 于 文新, ゾウ・クン, 花田 賢太郎, 鈴木 利治, きょう 建生, 柳澤 勝彦, 道川 誠

    Dementia Japan   18 ( 2 ) 134 - 134  2004年08月

  • 痴呆研究と創薬の展望 アルツハイマー病中核病変とコレステロール

    柳澤 勝彦, 道川 誠, 范 企文, 澤村 直哉, 松崎 勝巳

    基礎老化研究   26 ( 1 ) 6 - 6  2002年04月

  • Erratum: Cholesterol-dependent modulation of dendrite outgrowth and microtubule stability in cultured neurons (Journal of Neurochemistry (80) (178-190))

    Qi-Wen Fan, Wei Yu, Jian-Sheng Gong, Kun Zou, Naoya Sawamura, Takao Senda, Katsuhiko Yanagisawa, Makoto Michikawa

    Journal of Neurochemistry   80 ( 5 ) 940  2002年

    DOI

  • 脂質代謝とアルツハイマー病の分子病理

    柳澤 勝彦, 道川 誠, 林 秀樹, 澤村 直哉, 松崎 勝巳

    神経化学   40 ( 2-3 ) 220 - 220  2001年09月

▼全件表示

産業財産権

受賞

  • 上原記念生命科学財団 研究奨励金

    2007年  

  • National Alliance for Research on Schizophrenia & Depression (NARSAD), Young Investigator Award

    2005年  

共同研究・競争的資金等の研究課題

  • 新規統合失調症候補遺伝子産物CHRNA7の機能解析

    科学研究費助成事業(早稲田大学)  科学研究費助成事業(若手研究(B))

  • Arctic AβによるCHRNA7を介したアルツハイマー病発症の分子メカニズム

    科学研究費助成事業(早稲田大学)  科学研究費助成事業(基盤研究(C))

講演・口頭発表等

  • E3ユビキチンリガーゼCereblonは小胞体ストレス誘導性の異常なグリコーゲン集積を制御する

    川崎晃太郎, 飯田万由花, 川井聡子, 小野寺航, 朝日透, 朝日透, 澤村直哉, 澤村直哉

    日本分子生物学会年会プログラム・要旨集(Web)  

    発表年月: 2021年

    開催年月:
    2021年
     
     
  • 遠縁な配列間に対して焼きなまし法による分子系統樹の構築は有効である

    小野寺航, 朝日透, 朝日透, 澤村直哉, 澤村直哉

    日本分子生物学会年会プログラム・要旨集(Web)  

    発表年月: 2021年

    開催年月:
    2021年
     
     
  • 遠縁な種に対して有効な焼きなまし法による分子系統樹構築法の提案

    小野寺航, 朝日透, 朝日透, 澤村直哉, 澤村直哉

    日本進化学会大会プログラム・講演要旨集(Web)  

    発表年月: 2021年

    開催年月:
    2021年
     
     
  • 微小管結合タンパク質タウの分子進化解析

    高田海冴, 小野寺航, 朝日透, 朝日透, 澤村直哉, 澤村直哉

    日本進化学会大会プログラム・講演要旨集(Web)  

    発表年月: 2021年

    開催年月:
    2021年
     
     
  • APPファミリーの分子進化解析により明らかになったAPLP1の神経系に特殊化した進化

    小野寺航, 朝日透, 朝日透, 澤村直哉

    日本進化学会大会プログラム・講演要旨集(Web)  

    発表年月: 2019年

    開催年月:
    2019年
     
     
  • 哺乳類APLP1のシナプス接着因子としての進化可能性

    小野寺航, 朝日透, 朝日透, 澤村直哉

    日本分子生物学会年会プログラム・要旨集(Web)  

    発表年月: 2019年

    開催年月:
    2019年
     
     
  • E3ユビキチンリガーゼ複合体構成因子Cereblonの分子進化速度解析による機能的残基の同定と機能解析

    小野寺航, 朝日透, 朝日透, 澤村直哉

    日本進化学会大会プログラム・講演要旨集(Web)  

    発表年月: 2018年08月

  • 重度精神遅滞を引き起こすC391R Cereblonの分子機構

    川谷友郎, 朝日透, 朝日透, 澤村直哉

    日本分子生物学会年会プログラム・要旨集(Web)  

    発表年月: 2018年

  • 光遺伝学的手法の導入はパーキンソン病モデルショウジョウバエのドーパミン神経活動を改善する

    井下強, 孟紅蕊, 原清敬, 澤村直哉, 澤村直哉, 今居譲, 今居譲, 服部信孝, 服部信孝, 服部信孝

    日本分子生物学会年会プログラム・要旨集(Web)  

    発表年月: 2018年

  • Cereblonによるアミロイド前駆体タンパク質の分解機構の解析

    栗原知隆, 朝日透, 朝日透, 澤村直哉

    日本分子生物学会年会プログラム・要旨集(Web)  

    発表年月: 2018年

  • 分子進化速度解析によるAPPファミリーの差別化された機能の推定

    小野寺航, 朝日透, 朝日透, 澤村直哉

    日本分子生物学会年会プログラム・要旨集(Web)  

    発表年月: 2018年

  • 哺乳類Cereblonの分子進化速度解析による新規機能的サイトの同定

    小野寺航, 朝日透, 朝日透, 澤村直哉

    日本生化学会大会(Web)  

    発表年月: 2017年12月

  • 精神遅滞原因候補遺伝子cereblonの分子進化速度解析による機能的サイトの解明

    小野寺航, 朝日透, 朝日透, 澤村直哉

    日本進化学会大会プログラム・講演要旨集(Web)  

    発表年月: 2017年08月

  • CereblonのLonプロテアーゼとしての機能解析

    片岡孝介, 朝日透, 朝日透, 澤村直哉, 澤村直哉

    日本分子生物学会年会プログラム・要旨集(Web)  

    発表年月: 2016年

  • CereblonによるMeis2の転写制御機構の解析

    定方春樹, 和田丈慶, 朝日透, 朝日透, 澤村直哉, 澤村直哉

    日本分子生物学会年会プログラム・要旨集(Web)  

    発表年月: 2016年

  • 小胞体ストレスに着目したセレブロンの機能解析

    川井聡子, 朝日透, 朝日透, 澤村直哉, 澤村直哉

    日本分子生物学会年会プログラム・要旨集(Web)  

    発表年月: 2016年

  • サリドマイドの脳虚血に対する神経保護効果の分子メカニズム

    藤原美紅, 山田まりこ, 林秀樹, 山田春佳, 高木教夫, 朝日透, 朝日透, 澤村直哉, 澤村直哉

    日本分子生物学会年会プログラム・要旨集(Web)  

    発表年月: 2016年

  • CereblonのLonプロテアーゼとしての役割

    片岡孝介, 朝日透, 朝日透, 澤村直哉, 澤村直哉

    日本ミトコンドリア学会年会要旨集  

    発表年月: 2015年11月

  • サリドマイドによるエナンチオ特異的なAMPK活性調節メカニズムの解明

    藤原美紅, 山田春佳, 朝日透, 朝日透, 澤村直哉, 澤村直哉

    シンポジウム「モレキュラー・キラリティー」講演要旨集  

    発表年月: 2015年06月

  • 精神遅滞候補遺伝子産物セレブロンのアグリソームへの集積と細胞死保護効果

    松本広大, 松本広大, 若林慧, 山田春佳, 朝日透, 朝日透, 澤村直哉, 澤村直哉

    日本細胞生物学会大会要旨集  

    発表年月: 2015年06月

  • 精神遅滞候補遺伝子産物セレブロンのミトコンドリアにおける機能解析

    片岡孝介, 朝日透, 朝日透, 澤村直哉, 澤村直哉

    日本細胞生物学会大会要旨集  

    発表年月: 2015年06月

  • イオンビームを用いたAu2+導入による生細胞への影響検証

    野間口達洋, 坂口雄紀, 澤村直哉, 谷井孝至, 品田賢宏, 朝日透

    応用物理学会春季学術講演会講演予稿集(CD-ROM)  

    発表年月: 2014年03月

  • 電界効果トランジスタを用いた凝集形態の異なるアミロイドβの検出

    小林万純, 秀島翔, 黒岩繁樹, 中西卓也, 澤村直哉, 朝日透, 逢坂哲彌

    電気化学会大会講演要旨集  

    発表年月: 2013年03月

  • 電界効果トランジスタを用いた凝集形態の異なるアミロイドβの検出

    小林万純, 秀島翔, 黒岩繁樹, 中西卓也, 澤村直哉, 朝日透, 逢坂哲彌

    Chemical Sensors  

    発表年月: 2013年03月

  • 有機ゲルマニウムGe‐132の投与による酸化ストレス抑制作用

    和田丈慶, 岩本久乃, 朝日透, 澤村直哉

    日本薬学会年会要旨集(CD-ROM)  

    発表年月: 2013年03月

  • 各種酸化ストレスに対するサリドマイドの神経細胞死抑制効果の解析

    大平浩史, 山田春佳, 朝日透, 澤村直哉

    日本生化学会大会(Web)  

    発表年月: 2012年12月

  • デルタロドプシンのミトコンドリア特異的発現:パーキンソン病治療への応用

    和田丈慶, 原清敬, 朝日透, 澤村直哉

    日本生化学会大会(Web)  

    発表年月: 2012年12月

  • CereblonはそのE3 ubiquitin ligase活性を介してaggresomeに局在する(Cereblon localizes at aggresomes through its E3 ubiquitin ligase activity)

    若林 慧, 山田 春佳, 朝日 透, 澤村 直哉

    日本生化学会大会プログラム・講演要旨集  

    発表年月: 2012年12月

  • サリドマイドとそのエナンチオマーによる神経保護作用の分子メカニズム

    山田春佳, 大平浩史, 若林慧, 朝日透, 澤村直哉

    日本薬学会年会要旨集  

    発表年月: 2012年03月

  • Aβ凝集時の足場としてのCHRNA7の役割

    キョウ 曄, 和田 丈慶, 朝日 透, 澤村 直哉

    日本薬学会年会要旨集  

    発表年月: 2012年03月

  • ポリL‐及びDL‐乳酸ナノシートの微細構造解析

    宇田川瑛弘, 大森衣里子, 川本裕子, 澤村直哉, 武岡真司, 朝日透

    応用物理学関係連合講演会講演予稿集(CD-ROM)  

    発表年月: 2012年02月

  • Aβ凝集時の足場としてのCHRNA7タンパクの役割(CHRNA7 as scaffold molecule for Aβ aggregation)

    きょ 曄, 和田 丈慶, 朝日 透, 澤村 直哉

    神経化学  

    発表年月: 2011年09月

  • 酸化ストレスに対するサリドマイドとそのエナンチオマーによる神経保護作用(Neuroprotective effect of thalidomide and its enantiomers against oxidative stress)

    山田 春佳, 大平 浩史, 朝日 透, 澤村 直哉

    神経化学  

    発表年月: 2011年09月

  • 高異方性コラーゲンシートの光学的性質

    中川鉄馬, 荻野禎之, 鈴木俊哉, 田中真人, 田中佑治, 大和雅之, 松尾光一, 澤村直哉, 朝日透

    シンポジウム「モレキュラー・キラリティー」講演要旨集  

    発表年月: 2011年05月

  • サリドマイドのエナンチオ選択的な神経細胞死抑制効果

    澤村直哉, 山田春佳, 朝日透

    シンポジウム「モレキュラー・キラリティー」講演要旨集  

    発表年月: 2011年05月

  • ポリL‐乳酸及びポリDL‐乳酸ナノシートの微細構造解析

    宇田川瑛弘, 大森衣里子, 石川和彦, 鈴木俊哉, 澤村直哉, 武岡真司, 朝日透

    シンポジウム「モレキュラー・キラリティー」講演要旨集  

    発表年月: 2011年05月

  • 培養哺乳類細胞における古細菌ロドプシンのミトコンドリア特異的発現(MITOCHONDRIA-SPECIFIC EXPRESSION OF ARCHAEBACTERIAL RHODOPSIN IN CULTURED MAMMALIAN CELLS)

    和田 丈慶, 原 清敬, 朝日 透, 澤村 直哉

    日本細胞生物学会大会講演要旨集  

    発表年月: 2011年05月

  • 神経保護におけるサリドマイドのエナンチオ特異的な影響(The enantiospecific effect of thalidomide in neuroprotection)

    山田 春佳, 朝日 透, 澤村 直哉

    日本細胞生物学会大会講演要旨集  

    発表年月: 2011年05月

  • ポリ(L)乳酸からなるナノシートの微細構造と機能の関係

    大森衣里子, 藤枝俊宣, 澤村直哉, 武岡真司, 朝日透

    シンポジウム「モレキュラー・キラリティー」講演要旨集  

    発表年月: 2010年07月

  • サリドマイドとそのエナンチオマーによる神経保護作用の解析

    澤村直哉, 山田春佳, 朝日透

    シンポジウム「モレキュラー・キラリティー」講演要旨集  

    発表年月: 2010年07月

  • スフィンゴ脂質によるアミロイド前駆体蛋白の代謝制御

    澤村 直哉, 高 美姫, 于 文新, ゾウ・クン, 花田 賢太郎, 鈴木 利治, きょう 建生, 柳澤 勝彦, 道川 誠

    Dementia Japan  

    発表年月: 2004年08月

  • アミロイドbeta-蛋白(Abeta)1-42による神経毒性に対するAbeta1-40の細胞保護作用の検討(Amyloid beta-Protein (Abeta) 1-40 Protects Neurons from Damage Induced by Abeta1-42 in Culture and in Rat Brain)

    Zou Kun, Kim Daesung, 垣尾 敦子, Byun Kyunghee, Gong Jian-Sheng, Kim Myeongju, 澤村 直哉, 西本 清一, 松崎 勝巳, Lee Bonghee, 柳澤 勝彦, 道川 誠

    神経化学  

    発表年月: 2003年08月

  • Aβ1-42によって誘導される神経毒性に対するAβ1-40の細胞保護作用の検討

    Zou Kun, Kim Daesung, Byun Kyunghee, Gong Jian-Sheng, Kim Myeongju, 澤村 直哉, Lee Bonghee, 柳澤 勝彦, 道川 誠

    Dementia Japan  

    発表年月: 2003年08月

  • ニーマンピック病C型モデル細胞におけるタウ蛋白のリン酸化の検討

    澤村 直哉, きょう 建生, Chang Ta-Yuan, 柳澤 勝彦, 道川 誠

    Dementia Japan  

    発表年月: 2002年08月

  • ヒトアポリポ蛋白E3-,E4-ノックインマウスから調整したアストロサイトにおけるアイソフォーム依存的コレステロール搬出機構の検討

    きょう 建生, 小林 まり子, 林 秀樹, 鄒 鶤, 澤村 直哉, 藤田 忍, 柳澤 勝彦, 道川 誠

    Dementia Japan  

    発表年月: 2002年08月

  • ニーマンピック病C型モデルマウスにおけるMAPKの活性化に伴うタウ蛋白の部位特異的なリン酸化

    澤村 直哉, きょう 建生, 二宮 治明, 大野 耕策, 柳澤 勝彦, 道川 誠

    Dementia Japan  

    発表年月: 2001年08月

  • 細胞内コレステロール量依存的タウ蛋白リン酸化調節の検討

    道川 誠, 范 企文, 澤村 直哉, 愈 い, 千田 隆夫, 柳澤 勝彦

    神経化学  

    発表年月: 2000年10月

  • ニーマンピック病C型モデルマウスにおけるタウ蛋白のリン酸化の検討

    澤村 直哉, きょう 建生, 柳澤 勝彦, 道川 誠

    神経化学  

    発表年月: 2000年10月

  • 凝集したAmyloid β-proteinは神経細胞におけるコレステロール代謝に大きな影響を及ぼす

    きょう 建生, 澤村 直哉, 范 企文, 柳澤 勝彦, 道川 誠

    神経化学  

    発表年月: 2000年10月

  • 変異型presenilin 2トランスジェニックマウス脳内低密度膜ドメインにおけるAβ42の蓄積

    澤村 直哉, 小山 文隆, 森島 真帆, 井原 康夫

    神経化学  

    発表年月: 1999年09月

  • 変異型presenilin2トランスジェニックマウス脳内での加齢に伴うAβ42産生の増加

    澤村 直哉, 小山 文隆, 小林 喜美男, 森島 真帆, 倉持 隆司, 伊藤 守, 富田 泰輔, 丸山 敬, 西道 隆臣, 岩坪 威

    Dementia Japan  

    発表年月: 1998年09月

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