2024/10/07 更新

写真a

アンドウ シヨウイチロウ
安藤 昭一朗
ANDO Shoichiro
所属
医歯学総合病院 脳神経内科 助教
職名
助教
外部リンク

学位

  • 学士(医学) ( 2013年3月   新潟大学 )

研究キーワード

  • 脳小血管病

研究分野

  • ライフサイエンス / 神経内科学  / 脳小血管病

経歴(researchmap)

  • 新潟大学脳研究所   脳神経内科   助教

    2022年4月 - 現在

      詳細を見る

    国名:日本国

    researchmap

経歴

  • 新潟大学   医歯学総合病院 脳神経内科   助教

    2022年4月 - 現在

  • 新潟大学   脳研究所   特任助教

    2021年4月 - 2021年9月

学歴

  • 新潟大学   大学院医歯学総合研究科

    2018年4月 - 2022年3月

      詳細を見る

    国名: 日本国

    researchmap

  • 新潟大学   医学部   医学科

    2007年4月 - 2013年3月

      詳細を見る

    国名: 日本国

    researchmap

所属学協会

 

論文

  • Inherited C-terminal TREX1 variants disrupt homology-directed repair to cause senescence and DNA damage phenotypes in Drosophila, mice, and humans

    Samuel D. Chauvin, Shoichiro Ando, Joe A. Holley, Atsushi Sugie, Fang R. Zhao, Subhajit Poddar, Rei Kato, Cathrine A. Miner, Yohei Nitta, Siddharth R. Krishnamurthy, Rie Saito, Yue Ning, Yuya Hatano, Sho Kitahara, Shin Koide, W. Alexander Stinson, Jiayuan Fu, Nehalee Surve, Lindsay Kumble, Wei Qian, Oleksiy Polishchuk, Prabhakar S. Andhey, Cindy Chiang, Guanqun Liu, Ludovic Colombeau, Raphaël Rodriguez, Nicolas Manel, Akiyoshi Kakita, Maxim N. Artyomov, David C. Schultz, P. Toby Coates, Elisha D. O. Roberson, Yasmine Belkaid, Roger A. Greenberg, Sara Cherry, Michaela U. Gack, Tristan Hardy, Osamu Onodera, Taisuke Kato, Jonathan J. Miner

    Nature Communications   15 ( 1 )   2024年6月

     詳細を見る

    掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    Abstract

    Age-related microangiopathy, also known as small vessel disease (SVD), causes damage to the brain, retina, liver, and kidney. Based on the DNA damage theory of aging, we reasoned that genomic instability may underlie an SVD caused by dominant C-terminal variants in TREX1, the most abundant 3′−5′ DNA exonuclease in mammals. C-terminal TREX1 variants cause an adult-onset SVD known as retinal vasculopathy with cerebral leukoencephalopathy (RVCL or RVCL-S). In RVCL, an aberrant, C-terminally truncated TREX1 mislocalizes to the nucleus due to deletion of its ER-anchoring domain. Since RVCL pathology mimics that of radiation injury, we reasoned that nuclear TREX1 would cause DNA damage. Here, we show that RVCL-associated TREX1 variants trigger DNA damage in humans, mice, and Drosophila, and that cells expressing RVCL mutant TREX1 are more vulnerable to DNA damage induced by chemotherapy and cytokines that up-regulate TREX1, leading to depletion of TREX1-high cells in RVCL mice. RVCL-associated TREX1 mutants inhibit homology-directed repair (HDR), causing DNA deletions and vulnerablility to PARP inhibitors. In women with RVCL, we observe early-onset breast cancer, similar to patients with BRCA1/2 variants. Our results provide a mechanistic basis linking aberrant TREX1 activity to the DNA damage theory of aging, premature senescence, and microvascular disease.

    DOI: 10.1038/s41467-024-49066-7

    researchmap

    その他リンク: https://www.nature.com/articles/s41467-024-49066-7

  • Missense Variants in COL4A1/2 Are Associated with Cerebral Aneurysms: A Case Report and <span aria-describedby="tippy-31">Literature Review

    Masahiro Uemura, Natsuki Tanaka, Shoichiro Ando, Takehiko Yanagihara, Osamu Onodera

    Neurology International   2023年12月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    DOI: 10.20944/preprints202312.1336.v1

    researchmap

  • Inappropriate interpretation of non-pathogenic HTRA1 variant as pathogenic. 国際誌

    Masahiro Uemura, Sho Kitahara, Taisuke Kato, Hiroaki Nozaki, Shoichiro Ando, Tomohiko Ishihara, Osamu Onodera

    Annals of clinical and translational neurology   10 ( 7 )   1261 - 1262   2023年7月

     詳細を見る

    記述言語:英語  

    DOI: 10.1002/acn3.51817

    PubMed

    researchmap

  • Heterogenous Genetic, Clinical, and Imaging Features in Patients with Neuronal Intranuclear Inclusion Disease Carrying NOTCH2NLC Repeat Expansion

    Yusran Ady Fitrah, Yo Higuchi, Norikazu Hara, Takayoshi Tokutake, Masato Kanazawa, Kazuhiro Sanpei, Tomone Taneda, Akihiko Nakajima, Shin Koide, Shintaro Tsuboguchi, Midori Watanabe, Junki Fukumoto, Shoichiro Ando, Tomoe Sato, Yohei Iwafuchi, Aki Sato, Hideki Hayashi, Takanobu Ishiguro, Hayato Takeda, Toshiaki Takahashi, Nobuyoshi Fukuhara, Kensaku Kasuga, Akinori Miyashita, Osamu Onodera, Takeshi Ikeuchi

    Brain Sciences   13 ( 6 )   955 - 955   2023年6月

     詳細を見る

    掲載種別:研究論文(学術雑誌)   出版者・発行元:MDPI AG  

    Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disorder that is caused by the abnormal expansion of non-coding trinucleotide GGC repeats in NOTCH2NLC. NIID is clinically characterized by a broad spectrum of clinical presentations. To date, the relationship between expanded repeat lengths and clinical phenotype in patients with NIID remains unclear. Thus, we aimed to clarify the genetic and clinical spectrum and their association in patients with NIID. For this purpose, we genetically analyzed Japanese patients with adult-onset NIID with characteristic clinical and neuroimaging findings. Trinucleotide repeat expansions of NOTCH2NLC were examined by repeat-primed and amplicon-length PCR. In addition, long-read sequencing was performed to determine repeat size and sequence. The expanded GGC repeats ranging from 94 to 361 in NOTCH2NLC were found in all 15 patients. Two patients carried biallelic repeat expansions. There were marked heterogenous clinical and imaging features in NIID patients. Patients presenting with cerebellar ataxia or urinary dysfunction had a significantly larger GGC repeat size than those without. This significant association disappeared when these parameters were compared with the total trinucleotide repeat number. ARWMC score was significantly higher in patients who had a non-glycine-type trinucleotide interruption within expanded poly-glycine motifs than in those with a pure poly-glycine expansion. These results suggested that the repeat length and sequence in NOTCH2NLC may partly modify some clinical and imaging features of NIID.

    DOI: 10.3390/brainsci13060955

    researchmap

  • High frequency of<i>HTRA1</i>AND<i>ABCC6</i>mutations in Japanese patients with adult-onset cerebral small vessel disease

    Masahiro Uemura, Yuya Hatano, Hiroaki Nozaki, Shoichiro Ando, Hajime Kondo, Akira Hanazono, Akira Iwanaga, Hiroyuki Murota, Yosuke Osakada, Masato Osaki, Masato Kanazawa, Mitsuyasu Kanai, Yoko Shibata, Reiko Saika, Tadashi Miyatake, Hitoshi Aizawa, Takeshi Ikeuchi, Hidekazu Tomimoto, Ikuko Mizuta, Toshiki Mizuno, Tomohiko Ishihara, Osamu Onodera

    Journal of Neurology, Neurosurgery &amp; Psychiatry   jnnp - 2022   2022年10月

     詳細を見る

    掲載種別:研究論文(学術雑誌)   出版者・発行元:BMJ  

    Background

    This study aimed to clarify the frequency and clinical features of monogenic cerebral small vessel disease (mgCSVD) among patients with adult-onset severe CSVD in Japan.

    Methods

    This study included patients with adult-onset severe CSVD with an age of onset ≤55 years (group 1) or &gt;55 years and with a positive family history (group 2). After conducting conventional genetic tests forNOTCH3andHTRA1, whole-exome sequencing was performed on undiagnosed patients. Patients were divided into two groups according to the results of the genetic tests: monogenic and undetermined. The clinical and imaging features were compared between the two groups.

    Results

    Group 1 and group 2 included 75 and 31 patients, respectively. In total, 30 patients hadNOTCH3mutations, 11 patients hadHTRA1mutations, 6 patients hadABCC6mutations, 1 patient had aTREX1mutation, 1 patient had aCOL4A1mutation and 1 patient had aCOL4A2mutation. The total frequency of mutations inNOTCH3,HTRA1andABCC6was 94.0% in patients with mgCSVD. In group 1, the frequency of a family history of first relatives, hypertension and multiple lacunar infarctions (LIs) differed significantly between the two groups (monogenic vs undetermined; family history of first relatives, 61.0% vs 25.0%, p=0.0015; hypertension, 34.1% vs 63.9%, p=0.0092; multiple LIs, 87.8% vs 63.9%, p=0.0134).

    Conclusions

    More than 90% of mgCSVDs were diagnosed by screening forNOTCH3,HTRA1andABCC6. The target sequences for these three genes may efficiently diagnose mgCSVD in Japanese patients.

    DOI: 10.1136/jnnp-2022-329917

    researchmap

  • Candesartan prevents arteriopathy progression in cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy model. 査読 国際誌

    Taisuke Kato, Ri-Ichiroh Manabe, Hironaka Igarashi, Fuyuki Kametani, Sachiko Hirokawa, Yumi Sekine, Natsumi Fujita, Satoshi Saito, Yusuke Kawashima, Yuya Hatano, Shoichiro Ando, Hiroaki Nozaki, Akihiro Sugai, Masahiro Uemura, Masaki Fukunaga, Toshiya Sato, Akihide Koyama, Rie Saito, Atsushi Sugie, Yasuko Toyoshima, Hirotoshi Kawata, Shigeo Murayama, Masaki Matsumoto, Akiyoshi Kakita, Masato Hasegawa, Masafumi Ihara, Masato Kanazawa, Masatoyo Nishizawa, Shoji Tsuji, Osamu Onodera

    The Journal of clinical investigation   131 ( 22 )   2021年11月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Cerebral small vessel disease (CSVD) causes dementia and gait disturbance due to arteriopathy. Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a hereditary form of CSVD caused by loss of high-temperature requirement A1 (HTRA1) serine protease activity. In CARASIL, arteriopathy causes intimal thickening, smooth muscle cell (SMC) degeneration, elastic lamina splitting, and vasodilation. The molecular mechanisms were proposed to involve the accumulation of matrisome proteins as substrates or abnormalities in transforming growth factor β (TGF-β) signaling. Here, we show that HTRA1-/- mice exhibited features of CARASIL-associated arteriopathy: intimal thickening, abnormal elastic lamina, and vasodilation. In addition, the mice exhibited reduced distensibility of the cerebral arteries and blood flow in the cerebral cortex. In the thickened intima, matrisome proteins, including the hub protein fibronectin (FN) and latent TGF-β binding protein 4 (LTBP-4), which are substrates of HTRA1, accumulated. Candesartan treatment alleviated matrisome protein accumulation and normalized the vascular distensibility and cerebral blood flow. Furthermore, candesartan reduced the mRNA expression of Fn1, Ltbp-4, and Adamtsl2, which are involved in forming the extracellular matrix network. Our results indicate that these accumulated matrisome proteins may be potential therapeutic targets for arteriopathy in CARASIL.

    DOI: 10.1172/JCI140555

    PubMed

    researchmap

  • Corrigendum: HTRA1 Mutations Identified in Symptomatic Carriers Have the Property of Interfering the Trimer-Dependent Activation Cascade (Front. Neurol., (2019), 10, (693), 10.3389/fneur.2019.00693)

    Masahiro Uemura, Hiroaki Nozaki, Akihide Koyama, Naoko Sakai, Shoichiro Ando, Masato Kanazawa, Taisuke Kato, Osamu Onodera

    Frontiers in Neurology   12   2021年9月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Frontiers Media S.A.  

    In the original article, there were mistakes in Figures 1 and 3 as published. The multiplier of the unit for protease activity was incorrect. The correct value is 10 to the third power. The corrected Figures 1 and 3 appear below. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.

    DOI: 10.3389/fneur.2021.756038

    Scopus

    researchmap

  • [Rethinking Lacunar Stroke: Beyond Fisher's Curse].

    Osamu Onodera, Masahiro Uemura, Shoichiro Ando, Hideki Hayashi, Masato Kanazawa

    Brain and nerve = Shinkei kenkyu no shinpo   73 ( 9 )   991 - 998   2021年9月

     詳細を見る

    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    Lipohyalinosis is an important concept in the independence of lacunar stroke; however, its role has been overemphasized and has led to much confusion in the understanding of lacunar stroke. Classical lipohyalinosis has declined following the widespread availability of antihypertensive therapy, and lacunar stroke secondary to age-related hyaline atherosclerosis is more commonly observed in clinical practice. Clinically diagnosed lacunar stroke is associated with several etiopathogenetic contributors. Excluding cardiogenic embolism, lacunar stroke can be categorized based on the detection of an atheroma. Atheroma imaging is possible in recent years, and strokes that are not associated with an atheroma are shown to present with deep white matter hyperintensity on MRI. Additionally, risk gene analysis has confirmed a group of risk genes associated with the extracellular matrix in lacunar stroke with white matter hyperintensity on MRI. These findings suggest the role of a variety of etiopathogenetic mechanisms underlying lacunar stroke and that lacunar stroke with deep white matter hyperintensity on MRI may be attributable to unique pathogenetic contributors. This group is known to be strongly associated with genetic contributors. Hopefully, lacunar stroke will be diagnosed from this perspective with the development of interventional strategies tailored to the pathogenesis of this condition.

    DOI: 10.11477/mf.1416201876

    PubMed

    researchmap

  • Correction to: A novel splicing variant of ANXA11 in a patient with amyotrophic lateral sclerosis: histologic and biochemical features. 国際誌

    Makoto Sainouchi, Yuya Hatano, Mari Tada, Tomohiko Ishihara, Shoichiro Ando, Taisuke Kato, Jun Tokunaga, Gaku Ito, Hiroaki Miyahara, Yasuko Toyoshima, Akio Yokoseki, Tetsutaro Ozawa, Kohei Akazawa, Osamu Onodera, Akiyoshi Kakita

    Acta neuropathologica communications   9 ( 1 )   115 - 115   2021年6月

     詳細を見る

  • A novel splicing variant of ANXA11 in a patient with amyotrophic lateral sclerosis: histologic and biochemical features. 国際誌

    Makoto Sainouchi, Yuya Hatano, Mari Tada, Tomohiko Ishihara, Shoichiro Ando, Taisuke Kato, Jun Tokunaga, Gaku Ito, Hiroaki Miyahara, Yasuko Toyoshima, Akio Yokoseki, Tetsutaro Ozawa, Kohei Akazawa, Osamu Onodera, Akiyoshi Kakita

    Acta neuropathologica communications   9 ( 1 )   106 - 106   2021年6月

     詳細を見る

  • ゲノム編集による遺伝子サイレンシングを用いたDRPLA治療戦略

    安藤 昭一朗, 加藤 泰介, 小池 佑佳, 廣川 祥子, 小林 憲太, 辻 省次, 小野寺 理

    Dementia Japan   34 ( 4 )   531 - 531   2020年10月

     詳細を見る

    記述言語:日本語   出版者・発行元:(一社)日本認知症学会  

    researchmap

  • ゲノム編集による遺伝子サイレンシングを用いたDRPLA治療戦略

    安藤 昭一朗, 加藤 泰介, 小池 佑佳, 廣川 祥子, 小林 憲太, 辻 省次, 小野寺 理

    Dementia Japan   34 ( 4 )   531 - 531   2020年10月

     詳細を見る

    記述言語:日本語   出版者・発行元:(一社)日本認知症学会  

    researchmap

  • 【RAN翻訳と相分離で紐解くリピート病 くり返し配列の"長さ"が発症の原因となる謎に挑む】DNA、RNAを標的としたポリグルタミン病の新規治療戦略

    安藤 昭一朗, 加藤 泰介, 小野寺 理

    実験医学   38 ( 13 )   2191 - 2196   2020年8月

     詳細を見る

    記述言語:日本語   出版者・発行元:(株)羊土社  

    ポリグルタミン病(polyQ病)は、原因遺伝子のエキソン内に存在するCAGリピートの異常伸長により、伸長polyQ鎖を含む変異タンパク質が神経細胞内で凝集する疾患群である。これまで、polyQ病への治療は対症療法によるところが大きかった。しかし、近年の精力的な遺伝子治療研究への取り組みにより、polyQ病に対しても、進行抑制や発症予防につながるような治療アプローチが試みられ、すでにヒトでの臨床試験が行われているものもある。ここでは、アンチセンスオリゴヌクレオチドとCRISPR/Cas9システムを中心に、最近のpolyQ病に対する遺伝子治療研究の動向を概説する。(著者抄録)

    researchmap

  • Excessive Production of Transforming Growth Factor β1 Causes Mural Cell Depletion From Cerebral Small Vessels

    Taisuke Kato, Yumi Sekine, Hiroaki Nozaki, Masahiro Uemura, Shoichiro Ando, Sachiko Hirokawa, Osamu Onodera

    Frontiers in Aging Neuroscience   12   2020年6月

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    It is increasingly becoming apparent that cerebrovascular dysfunction contributes to the pathogenic processes involved in vascular dementia, Alzheimer’s disease, and other neurodegenerative disorders. Under these pathologic conditions, the degeneration of cerebral blood vessels is frequently accompanied by a loss of mural cells from the vascular walls. Vascular mural cells play pivotal roles in cerebrovascular functions, such as regulation of cerebral blood flow and maintenance of the blood-brain barrier (BBB). Therefore, cerebrovascular mural cell impairment is involved in the pathophysiology of vascular-related encephalopathies, and protecting these cells is essential for maintaining brain health. However, our understanding of the molecular mechanism underlying mural cell abnormalities is incomplete. Several reports have indicated that dysregulated transforming growth factor β (TGFβ) signaling is involved in the development of cerebral arteriopathies. These studies have specifically suggested the involvement of TGFβ overproduction. Although cerebrovascular toxicity via vascular fibrosis by extracellular matrix accumulation or amyloid deposition is known to occur with enhanced TGFβ production, whether increased TGFβ results in the degeneration of vascular mural cells in vivo remains unknown. Here, we demonstrated that chronic TGFβ1 overproduction causes a dropout of mural cells and reduces their coverage on cerebral vessels in both smooth muscle cells and pericytes. Mural cell degeneration was also accompanied by vascular luminal dilation. TGFβ1 overproduction in astrocytes significantly increased TGFβ1 content in the cerebrospinal fluid (CSF) and increased TGFβ signaling-regulated gene expression in both pial arteries and brain capillaries. These results indicate that TGFβ is an important effector that mediates mural cell abnormalities under pathological conditions related to cerebral arteriopathies.

    DOI: 10.3389/fnagi.2020.00151

    Scopus

    researchmap

  • Progressive Supranuclear Palsy with Predominant Cerebellar Ataxia 査読

    Shoichiro Ando, Masato Kanazawa, Osamu Onodera

    Journal of Movement Disorders   13 ( 1 )   20 - 26   2020年1月

     詳細を見る

    掲載種別:研究論文(学術雑誌)   出版者・発行元:The Korean Movement Disorder Society  

    DOI: 10.14802/jmd.19061

    researchmap

    その他リンク: http://e-jmd.org/journal/view.php?doi=10.14802/jmd.19061

  • Type IV collagen α1の3'UTRの新規変異による脳小血管病

    酒井 直子, 上村 昌寛, 加藤 泰介, 安藤 昭一朗, 野崎 洋明, 亀井 博之, 加藤 元博, 小野寺 理

    臨床神経学   59 ( Suppl. )   S327 - S327   2019年11月

     詳細を見る

    記述言語:日本語   出版者・発行元:(一社)日本神経学会  

    researchmap

  • 【脳の自浄システムとしてのアストロサイトとglymphaticシステム】神経脳小血管単位による排泄機構と疾病との関係

    安藤 昭一朗, 上村 昌寛, 小野寺 理

    Dementia Japan   33 ( 3 )   257 - 262   2019年9月

     詳細を見る

    記述言語:日本語   出版者・発行元:(一社)日本認知症学会  

    researchmap

  • 【嚥下障害と誤嚥性肺炎】主な神経疾患の嚥下障害の臨床 多系統萎縮症

    安藤 昭一朗, 金澤 雅人, 小野寺 理

    Clinical Neuroscience   37 ( 5 )   555 - 557   2019年5月

     詳細を見る

    記述言語:日本語   出版者・発行元:(株)中外医学社  

    researchmap

  • A case of chordoma presenting as recurrent bacterial meningitis with cerebrospinal fluid leakage 査読

    Shoichiro Ando, Hiroyuki Usuda, Yoshitaka Umeda, Maiko Umeda, Mutsuo Oyake, Nobuya Fujita

    Rinsho Shinkeigaku   59 ( 5 )   264 - 267   2019年

     詳細を見る

    掲載種別:研究論文(学術雑誌)   出版者・発行元:Societas Neurologica Japonica  

    DOI: 10.5692/clinicalneurol.cn-001272

    researchmap

  • A patient clinically diagnosed as multiple system atrophy harboring LRRK2 p.G2019S

    Shoichiro Ando, Takuya Konno, Tomohiko Ishihara, Hideki Hayashi, Natsumi Saito, Kenya Nishioka, Nobutaka Hattori, Zbigniew K. Wszolek, Osamu Onodera

    Clinical Parkinsonism & Related Disorders   1   100 - 101   2019年

     詳細を見る

    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/j.prdoa.2019.11.002

    researchmap

  • HTRA1 mutations identified in symptomatic carriers have the property of interfering the trimer-dependent activation cascade

    Masahiro Uemura, Hiroaki Nozaki, Akihide Koyama, Naoko Sakai, Shoichiro Ando, Masato Kanazawa, Taisuke Kato, Osamu Onodera

    Frontiers in Neurology   10 ( JUN )   2019年

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    Background: Mutations in the high-temperature requirement A serine peptidase 1 (HTRA1) cause cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). Most carriers for HTRA1 mutations are asymptomatic, but more than 10 mutations have been reported in symptomatic carriers. The molecular differences between the mutations identified in symptomatic carriers and mutations identified only in CARASIL patients are unclear. HTRA1 is a serine protease that forms homotrimers, with each HTRA1 subunit activating the adjacent HTRA1 via the sensor domain of loop 3 (L3) and the activation domain of loop D (LD). Previously, we analyzed four HTRA1 mutant proteins identified in symptomatic carriers and found that they were unable to form trimers or had mutations in the LD or L3 domain. The mutant HTRA1s with these properties are presumed to inhibit trimer-dependent activation cascade. Indeed, these mutant HTRA1s inhibited wild-type (WT) protease activity. In this study, we further analyzed 15 missense HTRA1s to clarify the molecular character of mutant HTRA1s identified in symptomatic carriers. Methods: We analyzed 12 missense HTRA1s identified in symptomatic carriers (hetero-HTRA1) and three missense HTRA1s found only in CARASIL (CARASIL-HTRA1). The protease activity of the purified recombinant mutant HTRA1s was measured using fluorescein isothiocyanate-labeled casein as substrate. Oligomeric structure was evaluated by size-exclusion chromatography. The protease activities of mixtures of WT with each mutant HTRA1 were also measured. Results: Five hetero-HTRA1s had normal protease activity and were excluded from further analysis. Four of the seven hetero-HTRA1s and one of the three CARASIL-HTRA1s were unable to form trimers. The other three hetero-HTRA1s had mutations in the LD domain. Together with our previous work, 10 of 11 hetero-HTRA1s and two of six CARASIL-HTRA1s were either defective in trimerization or had mutations in the LD or L3 domain (P = 0.006). By contrast, eight of 11 hetero-HTRA1s and two of six CARASIL-HTRA1 inhibited WT protease activity (P = 0.162). Conclusions: HTRA1 mutations identified in symptomatic carriers have the property of interfering the trimer-dependent activation cascade of HTRA1.

    DOI: 10.3389/fneur.2019.00693

    Scopus

    researchmap

  • MSA-Pと鑑別を要したPARK8の75歳女性例

    林 秀樹, 石原 智彦, 斎藤 奈つみ, 安藤 昭一朗, 小野寺 理

    臨床神経学   58 ( 12 )   779 - 779   2018年12月

     詳細を見る

    記述言語:日本語   出版者・発行元:(一社)日本神経学会  

    researchmap

  • 臨床経過および画像所見よりMSA-Pとの鑑別を要したPARK8の一例

    石原 智彦, 林 秀樹, 齋藤 奈つみ, 安藤 昭一朗, 小野寺 理

    パーキンソン病・運動障害疾患コングレスプログラム・抄録集   12回   100 - 100   2018年7月

     詳細を見る

    記述言語:日本語   出版者・発行元:Movement Disorder Society of Japan (MDSJ)  

    researchmap

  • A case of multiple cerebral hemorrhage caused by sudden increase of eosinophil in a patient with eosinophilic granulomatosis with polyangiitis

    Yumi Yamada, Shoichiro Ando, Yoshitaka Umeda, Maiko Umeda, Mutsuo Oyake, Nobuya Fujita

    Clinical Neurology   58 ( 9 )   565 - 569   2018年

     詳細を見る

    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Societas Neurologica Japonica  

    A 42-year-old woman with bronchial asthma was admitted to our hospital due to sensory dominant mononeuritis multiplex lasting for more than 6 months. At that time, her eosinophil count was 761/μl and her sural nerve biopsy showed no findings suggestive of vasculitis. Four months later, she experienced sudden convulsions and right hemiparesis due to left lobular parietal subcortical hemorrhage, when her eosinophil count was elevated to 3,257/μl. Numerous microbleeds and small infarctions were also detected in the intracerebral areas of different regions with MRI. Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic necrotizing vasculitis of the small vessels, commonly affecting the peripheral nerves. Subarachnoid hemorrhage in patients with EGPA is extremely rare. Steep elevation of the eosinophil count may release certain cytokines, causing cerebral hemorrhage.

    DOI: 10.5692/clinicalneurol.cn-001188

    Scopus

    PubMed

    researchmap

▶ 全件表示

MISC

  • 遺伝性脳小血管病モデルから見えてきたmatrisomeの破綻と治療法の展望

    加藤泰介, 眞鍋理一郎, 五十嵐博中, 亀谷富由樹, 齊藤聡, 畠野雄也, 安藤昭一朗, 福永雅喜, 佐藤俊哉, 齋藤理恵, 豊島靖子, 河田浩敏, 村山繁雄, 柿田明美, 長谷川成人, 猪原匡史, 西澤正豊, 辻省次, 小野寺理

    Dementia Japan   36 ( 4 )   2022年

     詳細を見る

  • Matrisomeの擾乱から見た脳小血管病の分子病態と治療法への展望

    加藤泰介, 眞鍋理一郎, 五十嵐博中, 亀谷富由樹, 齊藤聡, 畠野雄也, 安藤昭一朗, 福永雅喜, 佐藤俊哉, 齋藤理恵, 豊島靖子, 河田浩敏, 村山繁雄, 柿田明美, 長谷川成人, 猪原匡史, 西澤正豊, 辻省次, 小野寺理

    Dementia Japan   36 ( 4 )   2022年

     詳細を見る

  • HTRA1-Related Cerebral Small Vessel Disease: A Review of the Literature

    Masahiro Uemura, Hiroaki Nozaki, Taisuke Kato, Akihide Koyama, Naoko Sakai, Shoichiro Ando, Masato Kanazawa, Nozomi Hishikawa, Yoshinori Nishimoto, Kiran Polavarapu, Atchayaram Nalini, Akira Hanazono, Daisuke Kuzume, Akihiro Shindo, Mohammad El-Ghanem, Arata Abe, Aki Sato, Mari Yoshida, Takeshi Ikeuchi, Ikuko Mizuta, Toshiki Mizuno, Osamu Onodera

    Frontiers in Neurology   11   2020年7月

     詳細を見る

    掲載種別:書評論文,書評,文献紹介等  

    Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is clinically characterized by early-onset dementia, stroke, spondylosis deformans, and alopecia. In CARASIL cases, brain magnetic resonance imaging reveals severe white matter hyperintensities (WMHs), lacunar infarctions, and microbleeds. CARASIL is caused by a homozygous mutation in high-temperature requirement A serine peptidase 1 (HTRA1). Recently, it was reported that several heterozygous mutations in HTRA1 also cause cerebral small vessel disease (CSVD). Although patients with heterozygous HTRA1-related CSVD (symptomatic carriers) are reported to have a milder form of CARASIL, little is known about the clinical and genetic differences between the two diseases. Given this gap in the literature, we collected clinical information on HTRA1-related CSVD from a review of the literature to help clarify the differences between symptomatic carriers and CARASIL and the features of both diseases. Forty-six symptomatic carriers and 28 patients with CARASIL were investigated. Twenty-eight mutations in symptomatic carriers and 22 mutations in CARASIL were identified. Missense mutations in symptomatic carriers are more frequently identified in the linker or loop 3 (L3)/loop D (LD) domains, which are critical sites in activating protease activity. The ages at onset of neurological symptoms/signs were significantly higher in symptomatic carriers than in CARASIL, and the frequency of characteristic extraneurological findings and confluent WMHs were significantly higher in CARASIL than in symptomatic carriers. As previously reported, heterozygous HTRA1-related CSVD has a milder clinical presentation of CARASIL. It seems that haploinsufficiency can cause CSVD among symptomatic carriers according to the several patients with heterozygous nonsense/frameshift mutations. However, the differing locations of mutations found in the two diseases indicate that distinct molecular mechanisms influence the development of CSVD in patients with HTRA1-related CSVD. These findings further support continued careful examination of the pathogenicity of mutations located outside the linker or LD/L3 domain in symptomatic carriers.

    DOI: 10.3389/fneur.2020.00545

    Scopus

    researchmap

  • Type IV collagen α1の3'UTRの新規変異による脳小血管病

    酒井 直子, 上村 昌寛, 加藤 泰介, 安藤 昭一朗, 野崎 洋明, 亀井 博之, 加藤 元博, 小野寺 理

    臨床神経学   59 ( Suppl. )   S327 - S327   2019年11月

     詳細を見る

    記述言語:日本語   出版者・発行元:(一社)日本神経学会  

    researchmap

  • 臨床経過および画像所見よりMSA-Pとの鑑別を要したPARK8の一例

    石原 智彦, 林 秀樹, 齋藤 奈つみ, 安藤 昭一朗, 小野寺 理

    パーキンソン病・運動障害疾患コングレスプログラム・抄録集   12回   100 - 100   2018年7月

     詳細を見る

    記述言語:日本語   出版者・発行元:Movement Disorder Society of Japan (MDSJ)  

    researchmap

  • 臨床ケース 再発性胸腺腫術後に腹壁の難治性疼痛を呈した重症筋無力症の44歳男性例

    山岸 拓磨, 佐治 越爾, 荻根沢 真也, 安藤 昭一郎, 茂木 崇秀, 他田 正義, 河内 泉, 小野寺 理

    神経免疫学   22 ( 1 )   106 - 106   2017年10月

     詳細を見る

    記述言語:日本語   出版者・発行元:日本神経免疫学会  

    researchmap

  • 臨床ケース 再発性胸腺腫術後に腹壁の難治性疼痛を呈した重症筋無力症の44歳男性例

    山岸 拓磨, 佐治 越爾, 荻根沢 真也, 安藤 昭一郎, 茂木 崇秀, 他田 正義, 河内 泉, 小野寺 理

    神経免疫学   22 ( 1 )   106 - 106   2017年10月

     詳細を見る

    記述言語:日本語   出版者・発行元:日本神経免疫学会  

    researchmap

▶ 全件表示

受賞

  • 第65回日本神経学会学術集会. 一般演題 最優秀ポスター賞(臨床部門).

    2024年5月   日本神経学会  

     詳細を見る

  • Best Poster Award

    2023年12月   Asia Pacific Stroke Conference  

     詳細を見る

共同研究・競争的資金等の研究

  • 白質脳症をきたす変異型TREX1によるDNA損傷毒性誘導機序とその抑制分子の解明

    研究課題/領域番号:22K20882

    2022年8月 - 2024年3月

    制度名:科学研究費助成事業

    研究種目:研究活動スタート支援

    提供機関:日本学術振興会

    安藤 昭一朗

      詳細を見る

    配分額:2860000円 ( 直接経費:2200000円 、 間接経費:660000円 )

    本研究の目的は、Retinal vasculopathy with cerebral leukoencephalopathy(RVCL)疾患変異TREX1による細胞毒性を低減するヒト遺伝子種を同定することである。この背景には、RVCL疾患変異TREX1が、DNA切断損傷を誘導し、細胞毒性を引き起こすことがある。
    RVCLショウジョウバエモデルを用いた、RNAiスクリーニングで見出した、表現型抑制遺伝子4種のヒトホモログ遺伝子が、RVCLヒト細胞モデルにおいて細胞毒性を抑制し得るかを検討した。
    まず、HEK293細胞株を対象に、Flp-in systemを用いて、RVCL疾患変異であるp.Val235GlyfsTer6(V235fs)ヒトTREX1遺伝子を挿入し、RVCLヒト細胞モデルを作製した。このモデル細胞はドキシサイクリン誘導性に変異TREX1を発現する。
    次に、このモデル細胞に、表現型抑制候補遺伝子のshort hairpin RNA(shRNA)をレンチウイルスベクターを用いて導入した。shRNAによる遺伝子発現抑制効果は、droplet digital PCR(ddPCR)によって発現量解析を行った。いずれの遺伝子も発現抑制できていることを確認した。
    そして、このshRNAを導入したRVCLヒト細胞モデルを対象に、ToxiLight bioassayを用いて、表現型抑制候補遺伝子の抑制により、RVCL疾患変異TREX1による細胞毒性が低減するか検証した。結果、候補遺伝子4種のうち、2種の遺伝子において、ネガティブコントロールと比較して、shRNA導入群での細胞死率が低下した。従って、これらの2遺伝子が、ヒト細胞においてもRVCL疾患変異TREX1の細胞毒性を低減させる可能性が示唆された。

    researchmap

 

担当経験のある授業科目(researchmap)

  • 臓器別講義「脳・神経系」

    2022年4月
    -
    現在
    機関名:新潟大学医学部医学科

     詳細を見る