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Tetsuya Akiyama

Section

Tohoku University Hospital

Job title

Assistant Professor

researchmap

https://researchmap.jp/tetakiyama

J-GLOBAL ID

201801021353786100

Profile

神経内科医として診療に従事しながら、筋萎縮性側索硬化症（ALS）や脊髄性筋萎縮症（SMA）を中心とした運動ニューロン疾患の病態解明と治療法開発を目指して研究を行っています。
2020年から2026年まで米国Stanford大学遺伝学教室のAaron D. Gitler研究室で、ALS・前頭側頭型認知症の分子病態研究。現在は東北大学において、Physician-Scientistとして臨床神経学と基礎研究を融合し、患者由来iPS細胞、オミックス解析、神経筋病理学的解析などを用いて、RNA代謝異常と軸索障害を軸とした研究を展開しています。「神経変性疾患の発症機構を理解し、新たな治療法へとつなげること」を目標としています。

Research History 2

2014/04 - 2014/09

仙台医療センター脳神経内科
2013/04 - 2014/04

東北大学病院脳神経内科

Education 2

Tohoku University　School of Medicine　Department of Neurology

2013/04 - 2017/09
Tohoku University　Faculty of Medicine　School of Medicine

2004/04 - 2010/03

Research Interests 7

軸索輸送
RNA代謝
ストレス顆粒
iPS細胞
脊髄筋萎縮症
運動ニューロン病
筋萎縮性側索硬化症

Research Areas 2

Life sciences / Neuroscience - general /
Life sciences / Neurology /

Awards 5

Stanford Training Program in Aging Research

2021/04　Stanford University
すばるの会論文賞

2020/07　すばるの会（東北大学医学部神経内科同窓会）
海外研究留学助成

2020/01　武田科学振興財団
医学部奨学賞（銀賞）

2020/01　東北大学
若手道場優秀発表賞

2019/07　日本神経科学会・日本神経化学会

Papers 42

Mitochonic acid 5 alleviates amyotrophic lateral sclerosis phenotypes via mitochondrial augmentation Peer-reviewed

Yoshitsugu Oikawa, Yuhan Luo, Naoki Suzuki, Tomoko Kasahara, Yoshiyasu Tongu, Yuki Yoshida, Tsukasa Tominari, Shogo Tanabe, Yoshiko Suto, Hitomi Kashiwagi, Saki Saito, Kensuke Ikeda, Chitose Suzuki, Arata Kuranaga, Tetsuya Akiyama, Satoru Morimoto, Yoshitsugu Aoki, Rieko Muramatsu, Tomoyoshi Soga, Masashi Aoki, Hideyuki Okano, Tetsuhiro Tanaka, Takaaki Abe, Erina Kuranaga, Takafumi Toyohara

JCI Insight　11　(18)　e200761　2026/09/22
Publisher: American Society for Clinical Investigation
DOI： 10.1172/jci.insight.200761 　

eISSN： 2379-3708

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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that urgently requires effective treatment. Mitochondrial dysfunction underlies ALS pathology and represents a potential therapeutic target. Here, we demonstrated the therapeutic potential of mitochonic acid 5 (MA-5), a novel mitochondria-targeted compound that ameliorated ALS phenotypes by enhancing mitochondrial function. In a Drosophila ALS model expressing a mutant human SOD1 (G85R), MA-5 significantly improved locomotor activity, with a trend toward restoration of mitochondrial integrity. In skin fibroblasts derived from ALS patients and motor neurons derived from induced pluripotent stem cells, MA-5 restored ATP production and increased mitochondrial motility. Multiomics analyses suggested that MA-5 modulated mitochondria-linked gene expression and downregulated the glycerophosphate shuttle, contributing to mitochondrial reactive oxygen species production. Transcriptomic analysis identified C7orf31 as a potential marker for monitoring the therapeutic effects of MA-5 and diagnosing ALS subtypes. These findings support MA-5 as a promising therapeutic candidate for ALS and propose C7orf31 as a potential biomarker for treatment monitoring and for disease subtyping.
Cracking a New Era of Therapeutic Development in ALS.

Tetsuya Akiyama, Masashi Aoki

The Tohoku journal of experimental medicine　2026/07/16

DOI： 10.1620/tjem.2026.J082 　
Cryptic splicing in synaptic and membrane excitability genes links TDP-43 loss to neuronal dysfunction

Caiwei Guo, Kuchuan Chen, Sarat Vatsavayai, Tetsuya Akiyama, Chang Liu, Yi Zeng, Odilia Sianto, Edith Yang, Juliane Bombosch, Rasheen Powell, Shannon Zhen, Shila Mekhoubad, Ryan D. Morrie, Georgiana Miller, Dragana Ilic, Moritz Boll, Euan Parnell, Peter Penzes, Noa Lipstein, Eric M. Green, Leonard Petrucelli, William W. Seeley, Aaron D. Gitler

Science Translational Medicine　2026/06/03

DOI： 10.1126/scitranslmed.aeb8517 　

ISSN： 2692-8205

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TDP-43 pathology is a defining pathological hallmark of multiple neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). A major feature of TDP-43 pathology is its nuclear depletion, leading to the aberrant inclusion of cryptic exons during RNA splicing. STMN2 and UNC13A have emerged as prominent TDP-43 splicing targets, but the broader impact of TDP-43-dependent cryptic splicing on neuronal function remains unclear. Here, we report new TDP-43 splicing targets critical for membrane excitability and synaptic function, including KALRN, RAP1GAP, SYT7 and KCNQ2. Using human stem cell-derived neurons, we show that TDP-43 reduction induces cryptic splicing and downregulation of these genes, resulting in impaired excitability and synaptic transmission. In postmortem brains from patients with FTD, these cryptic splicing events occur selectively in neurons with TDP-43 pathology. Importantly, suppressing individual cryptic splicing events using antisense oligonucleotides partially restores neuronal function, and combined targeting almost fully rescues the synaptic deficit caused by TDP-43 loss. Together, our findings provide evidence that cryptic splicing in these synaptic and membrane excitability genes is not only a downstream marker but instead a direct driver of neuronal dysfunction, establishing a mechanistic link between TDP-43 pathology and neurodegeneration in ALS and FTD.
Whole-genome 3D architectural screen reveals modulators of brain DNA structure. International-journal

Bibudha Parasar, Achuthan Raja Venkatesh, Jonathan Perera, Lucas Sosnick, Siavash Moghadami, Yunji Seo, Jenny Shi, Lynette Chan, Satoshi Takenawa, Tetsuya Akiyama, Odilia Sianto, Takeshi Uenaka, Angela Hadjipanayis, Marius Wernig, Aaron D Gitler, Longzhi Tan

bioRxiv : the preprint server for biology　2026/04/17

DOI： 10.64898/2026.04.15.718501 　

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Three-dimensional (3D) genome architecture is the foundation of gene regulation, and plays a critical role in normal physiology and disease. However, our understanding of its biochemical determinants has long been limited by technology: imaging-based screens only profile a small number of loci, while sequencing-based studies rarely exceed 100 samples or conditions. Here we present "in-plate chromosome conformation capture" (Plate-C), a high-throughput, cost-effective platform that profiles thousands of whole-genome architectures in a day. Plate-C enabled the first chemical screen for whole-genome structural changes-profiling 2,956 samples from 834 conditions across 5 neuronal and glial types, accompanied by 6,081 single cells using "easy diploid chromosome conformation capture" (Easy Dip-C) and 200,893 single-cell transcriptomes. We discovered that diverse, dose/time-dependent, and cell type/species-specific modes of DNA structural changes can be rapidly induced by manipulating epigenetic (HDAC, BET), metabolic (mTOR), proteostatic (UPR), developmental (GSK3/Wnt, Hedgehog), immune (cGAS/STING), and neurotransmission pathways. To validate our finding in vivo, we demonstrated in newborn mice that HDAC inhibition drives brain-wide genome rewiring within hours, highly correlated with changes in vitro and inducing a latent structural and transcriptional state orthogonal to normal differentiation. By enabling massively parallel profiling of whole-genome structures, Plate-C paves the way for systematic discovery of DNA folding principles to better understand and engineer the human genome in 3D.
A Novel Dysferlin-Binding Kinase CK2α Promotes Plasma Membrane Repair in Dysferlinopathy. International-journal

Naoko Nakamura, Naoki Suzuki, Shin-Ichiro Kanno, Rei Yamanaka, Hiroya Ono, Rumiko Izumi, Rui Muliang, Christian Borgo, Akiyuki Ohno, Ryuhei Harada, Saki Saito, Yukino Funayama, Kensuke Ikeda, Shio Mitsuzawa, Yasuaki Watanabe, Tomomi Shijo, Tetsuya Akiyama, Toshiaki Takahashi, Makoto Kanzaki, Shion Osana, Hitoshi Warita, Yoshitsugu Aoki, Satoru Ebihara, Mauro Salvi, Ryoichi Nagatomi, Akira Yasui, Katsuya Miyake, Masashi Aoki

FASEB journal : official publication of the Federation of American Societies for Experimental Biology　40　(6)　e71677　2026/03/31

DOI： 10.1096/fj.202500773RRR 　

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Dysferlinopathy is an adult-onset form of muscular dystrophy caused by mutations in the dysferlin gene and is inherited in an autosomal recessive manner. Dysferlin is primarily known for its role in plasma membrane repair. Although several proteins associated with dysferlin have been identified, many aspects of its signaling pathways and protein-protein interactions remain unclear. Here, we focused on the region between the third and fourth C2 domains, where frequent genetic mutations occur and functional domains are concentrated, and identified the protein kinase CK2α (formerly known as casein kinase 2) as a novel dysferlin-binding protein. CK2α was found to accumulate at membrane injury sites along with dysferlin in mouse skeletal muscle, and membrane repair was delayed in CK2α knockout cells. Furthermore, overexpression of CK2α in dysferlin-deficient mouse muscle led to improved membrane repair. Additionally, we revealed that CK2α plays a role in phosphorylating annexin A1, which is known to bind to dysferlin and is involved in plasma membrane repair. Our results indicated that CK2α controls membrane repair by participating in the phosphorylation of annexin A1. The molecular interplay among dysferlin, CK2α, and phosphorylated annexin A1 represents a novel therapeutic target for promoting membrane repair.
KIF5A downregulation in spinal muscular atrophy links axonal regeneration defects with ALS International-journal

Tetsuya Akiyama, Yi Zeng, Caiwei Guo, Olivia Gautier, Lauren S Koepke, Juliane Bombosch, Odilia Sianto, Jay P Ross, Phuong T Hoang, Luke Yuchen Zhao, Cole Spencer, Michelle Monje, John W Day, Aaron Gitler

JCI insight　2026/03/26

DOI： 10.1101/2025.07.11.664426 　

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<jats:p>Spinal muscular atrophy (SMA) is a devastating neuromuscular disorder caused by mutations in the Survival Motor Neuron 1 (SMN1) gene, leading to decreased SMN levels and motor neuron dysfunction. SMN-restoring therapies offer clinical benefit, but the downstream molecular consequences of SMN reduction remain incompletely understood. Here, we demonstrate that SMN deficiency results in downregulation of KIF5A in human neurons and in a mouse model of SMA. We provide evidence that reduced SMN levels impair axon regeneration, which is rescued by KIF5A overexpression and that the RNA-binding protein SMN functions to stabilize KIF5A mRNA. These findings provide evidence of a molecular link between SMA and ALS pathophysiology, highlighting KIF5A as a new SMN target. Our findings suggest SMN-independent interventions targeting KIF5A could represent a complementary therapeutic approach for SMA and other motor neuron diseases.</jats:p>
TDP-43 nuclear loss in FTD/ALS causes widespread alternative polyadenylation changes

Yi Zeng, Anastasiia Lovchykova, Tetsuya Akiyama, Stephanie L. Rayner, Vidhya Maheswari Jawahar, Chang Liu, Odilia Sianto, Caiwei Guo, Anna Calliari, Mercedes Prudencio, Dennis W. Dickson, Leonard Petrucelli, Aaron D. Gitler

Nature Neuroscience　2025/10/21

DOI： 10.1038/s41593-025-02049-3 　
ALS-associated RNA-binding proteins promote UNC13A transcription through REST downregulation

Yasuaki Watanabe, Naoki Suzuki, Tadashi Nakagawa, Masaki Hosogane, Tetsuya Akiyama, Naotoshi Kageyama, Yukino Funayama, Hitoshi Warita, Satoru Morimoto, Hideyuki Okano, Masashi Aoki, Keiko Nakayama

The EMBO Journal　2025/07/24
Publisher: Springer Science and Business Media LLC
DOI： 10.1038/s44318-025-00506-0 　

eISSN： 1460-2075

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Abstract Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by selective loss of motor neurons. Although multiple pathophysiological mechanisms have been identified, no comprehensive understanding of these heterogeneous processes has been achieved. The ALS-associated RNA-binding protein (RBP) TDP-43 has previously been shown to stabilize UNC13A mRNA by preventing cryptic exon inclusion. Here, we show that the ALS-associated RBPs MATR3, FUS, and hnRNPA1 regulate UNC13A expression by targeting the transcriptional repressor REST. These RBPs bind to and downregulate REST mRNA to promote UNC13A transcription. Loss of any of these RBPs in cultured cells or in iPSC-derived motor neurons carrying the ALS-causing FUS P525L mutation leads to REST overexpression, and the same is observed in motor neurons of individuals with familial or sporadic ALS. The functional convergence of four RBPs on the regulation of UNC13A expression underscores the important role of this process for synaptic integrity, and its association with ALS pathogenesis could be relevant for the development of new therapeutic agents.
Nonsense-mediated decay masks cryptic splicing events caused by TDP-43 loss

Yi Zeng, Odilia Sianto, Anastasiia Lovchykova, Chang Liu, Tetsuya Akiyama, Leonard Petrucelli, Aaron Gitler

2025/07/09

DOI： 10.1101/2025.07.09.664014 　

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<jats:title>Abstract</jats:title> <jats:p>In frontotemporal dementia and amyotrophic lateral sclerosis, the RNA-binding protein TDP-43 is lost from the nucleus, leading to cryptic exon inclusion events in dozens of neuronal genes. Here, we show that many cryptic splicing events have been missed by standard RNA-sequencing analyses because they are substrates for nonsense-mediated decay. By inhibiting nonsense-mediated decay in neurons we unmask hundreds of novel cryptic splicing events caused by TDP-43 depletion, providing a new picture to TDP-43 loss of function in neurons.</jats:p>
Updated Genetic Analysis of Japanese Familial ALS Patients Carrying SOD1 Variants Revealed Phenotypic Differences for Common Variants. International-journal

Ayumi Nishiyama, Tetsuya Niihori, Naoki Suzuki, Rumiko Izumi, Tetsuya Akiyama, Masaaki Kato, Ryo Funayama, Keiko Nakayama, Hitoshi Warita, Yoko Aoki, Masashi Aoki

Neurology. Genetics　10　(6)　e200196　2024/12

DOI： 10.1212/NXG.0000000000200196 　

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BACKGROUND AND OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is an adult-onset progressive neurodegenerative disease. Approximately 10% of ALS cases are familial, and more than 20 causative genes have been identified. As we have previously reported, SOD1 variants are the most common causes of familial ALS in Japan. Because antisense oligonucleotides for SOD1-linked ALS are being used in practical applications, the types of variants and the clinical features of patients need to be updated. METHODS: We consecutively recruited 160 families with familial ALS in Japan. We performed genetic analyses, focusing on SOD1-linked ALS as the most common in our cohort, updated their genotypes, and characterized clinical phenotypes. RESULTS: A total of 26 SOD1 variants in 56 patients and 49 families (30.6%) were collected, with the 3 most common (p.His47Arg [the conventional numbering; H46R], p.Leu127Ser [L126S], p.Asn87Ser [N86S]) accounting for 38.8% of all families. We also identified 2 novel variants (p.Ile36Phe [I35F] and p.Asn132Argfs*3 [N131Rfs*3]). The mean age at onset was 48.9 ± 12.2 (mean ± SD) years for all patients with SOD1-linked ALS. Lower limb onset comprised 70% of cases. The mean disease duration was 64.7 ± 82 months, and the median survival was 71.5 months. Some variants led to a relatively homogeneous phenotype, although clinical characteristics differed among types of variants and families. Patients with p.His47Arg (H46R) showed slower progression with lower limb onset and a predominance of lower motor neuron involvement. The p.Leu127Ser (L126S) variant led to varying degrees of progression in heterozygous or homozygous states and presented incomplete penetrance. Intrafamilial phenotypic differences were observed in families carrying p.Asn87Ser (N86S). Four variants (p.Cys7Gly [C6G], p.His44Arg [H43R], p.Leu85Val [L84V], and p.Cys147Arg [C146R]) were found to be associated with rapid disease progression. DISCUSSION: The genetic basis of familial ALS, at least for SOD1 variants, still differed by geographic and ethnic background. Understanding these clinical profiles will help optimize evaluation in targeted gene therapy worldwide and benefit efficient diagnosis, leading to precise application in clinical practice.
Genome-wide CRISPR screen reveals v-ATPase as a drug target to lower levels of ALS protein ataxin-2. International-journal

Garam Kim, Lisa Nakayama, Jacob A Blum, Tetsuya Akiyama, Steven Boeynaems, Meenakshi Chakraborty, Julien Couthouis, Eduardo Tassoni-Tsuchida, Caitlin M Rodriguez, Michael C Bassik, Aaron D Gitler

Cell reports　41　(4)　111508-111508　2022/10/25

DOI： 10.1016/j.celrep.2022.111508 　

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Mutations in the ataxin-2 gene (ATXN2) cause the neurodegenerative disorders amyotrophic lateral sclerosis (ALS) and spinocerebellar ataxia type 2 (SCA2). A therapeutic strategy using antisense oligonucleotides targeting ATXN2 has entered clinical trial in humans. Additional ways to decrease ataxin-2 levels could lead to cheaper or less invasive therapies and elucidate how ataxin-2 is normally regulated. Here, we perform a genome-wide fluorescence-activated cell sorting (FACS)-based CRISPR-Cas9 screen in human cells and identify genes encoding components of the lysosomal vacuolar ATPase (v-ATPase) as modifiers of endogenous ataxin-2 protein levels. Multiple FDA-approved small molecule v-ATPase inhibitors lower ataxin-2 protein levels in mouse and human neurons, and oral administration of at least one of these drugs-etidronate-is sufficient to decrease ataxin-2 in the brains of mice. Together, we propose v-ATPase as a drug target for ALS and SCA2 and demonstrate the value of FACS-based screens in identifying genetic-and potentially druggable-modifiers of human disease proteins.
Targeting RTN4/NoGo-Receptor reduces levels of ALS protein ataxin-2. International-journal

Caitlin M Rodriguez, Sophia C Bechek, Graham L Jones, Lisa Nakayama, Tetsuya Akiyama, Garam Kim, David E Solow-Cordero, Stephen M Strittmatter, Aaron D Gitler

Cell reports　41　(4)　111505-111505　2022/10/25

DOI： 10.1016/j.celrep.2022.111505 　

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Gene-based therapeutic strategies to lower ataxin-2 levels are emerging for the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and spinocerebellar ataxia type 2 (SCA2). Additional strategies to lower levels of ataxin-2 could be beneficial. Here, we perform a genome-wide arrayed small interfering RNA (siRNA) screen in human cells and identify RTN4R, the gene encoding the RTN4/NoGo-Receptor, as a potent modifier of ataxin-2 levels. RTN4R knockdown, or treatment with a peptide inhibitor, is sufficient to lower ataxin-2 protein levels in mouse and human neurons in vitro, and Rtn4r knockout mice have reduced ataxin-2 levels in vivo. We provide evidence that ataxin-2 shares a role with the RTN4/NoGo-Receptor in limiting axonal regeneration. Reduction of either protein increases axonal regrowth following axotomy. These data define the RTN4/NoGo-Receptor as a novel therapeutic target for ALS and SCA2 and implicate the targeting of ataxin-2 as a potential treatment following nerve injury.
TDP-43 represses cryptic exon inclusion in the FTD–ALS gene UNC13A

X. Rosa Ma, Mercedes Prudencio, Yuka Koike, Sarat C. Vatsavayai, Garam Kim, Fred Harbinski, Adam Briner, Caitlin M. Rodriguez, Caiwei Guo, Tetsuya Akiyama, H. Broder Schmidt, Beryl B. Cummings, David W. Wyatt, Katherine Kurylo, Georgiana Miller, Shila Mekhoubad, Nathan Sallee, Gemechu Mekonnen, Laura Ganser, Jack D. Rubien, Karen Jansen-West, Casey N. Cook, Sarah Pickles, Björn Oskarsson, Neill R. Graff-Radford, Bradley F. Boeve, David S. Knopman, Ronald C. Petersen, Dennis W. Dickson, James Shorter, Sua Myong, Eric M. Green, William W. Seeley, Leonard Petrucelli, Aaron D. Gitler

Nature　2022/02/23
Publisher: Springer Science and Business Media {LLC}
DOI： 10.1038/s41586-022-04424-7 　
Cracking the cryptic code in amyotrophic lateral sclerosis and frontotemporal dementia: Towards therapeutic targets and biomarkers. Invited

Tetsuya Akiyama, Yuka Koike, Leonard Petrucelli, Aaron D Gitler

Clinical and translational medicine　12　(5)　2022

DOI： 10.1002/ctm2.818 　

ISSN： 2001-1326

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Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two devastating human neurodegenerative diseases. A hallmark pathological feature of both diseases is the depletion of the RNA-binding protein TDP-43 from the nucleus in the brain and spinal cord of patients. A major function of TDP-43 is to repress the inclusion of cryptic exons during RNA splicing. When it becomes depleted from the nucleus in disease, this function is lost, and recently, several key cryptic splicing targets of TDP-43 have emerged, including STMN2, UNC13A, and others. UNC13A is a major ALS/FTD risk gene, and the genetic variations that increase the risk for disease seem to do so by making the gene more susceptible to cryptic exon inclusion when TDP-43 function is impaired. Here, we discuss the prospects and challenges of harnessing these cryptic splicing events as novel therapeutic targets and biomarkers. Deciphering this new cryptic code may be a touchstone for ALS and FTD diagnosis and treatment.
Identification of hub molecules of FUS-ALS by Bayesian gene regulatory network analysis of iPSC model: iBRN

Masahiro Nogami, Mitsuru Ishikawa, Atsushi Doi, Osamu Sano, Takefumi Sone, Tetsuya Akiyama, Masashi Aoki, Atsushi Nakanishi, Kazuhiro Ogi, Masato Yano, Hideyuki Okano

Neurobiology of Disease　155　2021/07

DOI： 10.1016/j.nbd.2021.105364 　

ISSN： 0969-9961

eISSN： 1095-953X
Reduced PHOX2B stability causes axonal growth impairment in motor neurons with TARDBP mutations

Shio Mitsuzawa, Naoki Suzuki, Tetsuya Akiyama, Mitsuru Ishikawa, Takefumi Sone, Jiro Kawada, Ryo Funayama, Matsuyuki Shirota, Hiroaki Mitsuhashi, Satoru Morimoto, Kensuke Ikeda, Tomomi Shijo, Akiyuki Ohno, Naoko Nakamura, Hiroya Ono, Risako Ono, Shion Osana, Tadashi Nakagawa, Ayumi Nishiyama, Rumiko Izumi, Shohei Kaneda, Yoshiho Ikeuchi, Keiko Nakayama, Teruo Fujii, Hitoshi Warita, Hideyuki Okano, Masashi Aoki

Stem Cell Reports　16　(6)　1527-1541　2021/06/08

DOI： 10.1016/j.stemcr.2021.04.021 　

ISSN： 2213-6711
Aberrant astrocytic expression of chondroitin sulfate proteoglycan receptors in a rat model of amyotrophic lateral sclerosis Peer-reviewed

Tomomi Shijo, Hitoshi Warita, Naoki Suzuki, Yasuo Kitajima, Kensuke Ikeda, Tetsuya Akiyama, Hiroya Ono, Shio Mitsuzawa, Ayumi Nishiyama, Rumiko Izumi, Masashi Aoki

Journal of Neuroscience Research　96　(2)　222-233　2021/02

DOI： 10.1002/jnr.24127 　

ISSN： 0360-4012

eISSN： 1097-4547
An Amyotrophic Lateral Sclerosis-Associated Mutant of C21ORF2 Is Stabilized by NEK1-Mediated Hyperphosphorylation and the Inability to Bind FBXO3 International-journal Peer-reviewed

Yasuaki Watanabe, Tadashi Nakagawa, Tetsuya Akiyama, Makiko Nakagawa, Naoki Suzuki, Hitoshi Warita, Masashi Aoki, Keiko Nakayama

iScience　23　(9)　101491-101491　2020/09/25

DOI： 10.1016/j.isci.2020.101491 　

eISSN： 2589-0042
【神経疾患治療の進歩2019】運動ニューロン疾患の治療の進歩

秋山徹也, 割田仁, 鈴木直輝, 青木正志

神経治療学　37　(5)　736-740　2020/09
Publisher: (一社)日本神経治療学会
ISSN： 0916-8443

eISSN： 2189-7824
【神経疾患治療の進歩2019】運動ニューロン疾患の治療の進歩

秋山徹也, 割田仁, 鈴木直輝, 青木正志

神経治療学　37　(5)　736-740　2020/09
Publisher: (一社)日本神経治療学会
ISSN： 0916-8443

eISSN： 2189-7824
Generation of an ALS human iPSC line KEIOi001-A from peripheral blood of a Charcot disease-affected patient carrying TARDBP p.N345K heterozygous SNP mutation. International-journal Peer-reviewed

Nicolas Leventoux, Satoru Morimoto, Kenju Hara, Shiho Nakamura, Fumiko Ozawa, Shio Mitsuzawa, Tetsuya Akiyama, Ayumi Nishiyama, Naoki Suzuki, Hitoshi Warita, Masashi Aoki, Hideyuki Okano

Stem cell research　47　101896-101896　2020/06/28

DOI： 10.1016/j.scr.2020.101896 　

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Amyotrophic Lateral Sclerosis is the most common motor neuron degenerative disease in adults, and TARDBP gene mutations have been reported to be involved in the pathogenesis. We present here how we generated the human induced pluripotent stem cell (hiPSC) line KEIOi001-A/SM4-4-5 from the peripheral blood of a 63-year-old male patient presenting the c.1035C > G heterozygous SNP mutation in the TARDBP gene locus. The established hiPSC line does not express the exogenous reprogramming factors oriP nor EBNA1 and shows no karyotypic abnormalities, while it expresses pluripotent stem cell markers, presents the SNP mutation and is capable of three-germ layers differentiation in vitro.
AMPK Complex Activation Promotes Sarcolemmal Repair in Dysferlinopathy Peer-reviewed

Hiroya Ono, Naoki Suzuki, Shin ichiro Kanno, Genri Kawahara, Rumiko Izumi, Toshiaki Takahashi, Yasuo Kitajima, Shion Osana, Naoko Nakamura, Tetsuya Akiyama, Kensuke Ikeda, Tomomi Shijo, Shio Mitsuzawa, Ryoichi Nagatomi, Nobukazu Araki, Akira Yasui, Hitoshi Warita, Yukiko K. Hayashi, Katsuya Miyake, Masashi Aoki

Molecular Therapy　28　(4)　1133-1153　2020/04

DOI： 10.1016/j.ymthe.2020.02.006 　

ISSN： 1525-0016

eISSN： 1525-0024
Omics Approach to Axonal Dysfunction of Motor Neurons in Amyotrophic Lateral Sclerosis (ALS) International-journal Peer-reviewed

Naoki Suzuki, Tetsuya Akiyama, Hitoshi Warita, Masashi Aoki

Frontiers in Neuroscience　14　194-194　2020/03/25

DOI： 10.3389/fnins.2020.00194 　

ISSN： 1662-4548

eISSN： 1662-453X
Extracellular α-synuclein enters dopaminergic cells by modulating flotillin-1–assisted dopamine transporter endocytosis International-journal Peer-reviewed

Junpei Kobayashi, Takafumi Hasegawa, Naoto Sugeno, Shun Yoshida, Tetsuya Akiyama, Koki Fujimori, Hiroyasu Hatakeyama, Yasuo Miki, Arata Tomiyama, Yasushi Kawata, Mitsunori Fukuda, Ichiro Kawahata, Tohru Yamakuni, Michinori Ezura, Akio Kikuchi, Toru Baba, Atsushi Takeda, Makoto Kanzaki, Koichi Wakabayashi, Hideyuki Okano, Masashi Aoki

FASEB Journal　33　(9)　10240-10256　2019/09/01

DOI： 10.1096/fj.201802051R 　

ISSN： 0892-6638

eISSN： 1530-6860
Aberrant axon branching via Fos-B dysregulation in FUS-ALS motor neurons International-journal Peer-reviewed

Tetsuya Akiyama, Naoki Suzuki, Mitsuru Ishikawa, Koki Fujimori, Takefumi Sone, Jiro Kawada, Ryo Funayama, Fumiyoshi Fujishima, Shio Mitsuzawa, Kensuke Ikeda, Hiroya Ono, Tomomi Shijo, Shion Osana, Matsuyuki Shirota, Tadashi Nakagawa, Yasuo Kitajima, Ayumi Nishiyama, Rumiko Izumi, Satoru Morimoto, Yohei Okada, Takayuki Kamei, Mayumi Nishida, Masahiro Nogami, Shohei Kaneda, Yoshiho Ikeuchi, Hiroaki Mitsuhashi, Keiko Nakayama, Teruo Fujii, Hitoshi Warita, Hideyuki Okano, Masashi Aoki

EBioMedicine　45　362-378　2019/07

DOI： 10.1016/j.ebiom.2019.06.013 　

eISSN： 2352-3964
Review/Advances in Neurological Therapeutics (2018). Motor neuron disease Invited

Akiyama Tetsuya, Suzuki Naoki, Warita Hitoshi, Aoki Masashi

Neurological Therapeutics　36　(5)　584-587　2019
Publisher: Japanese Society of Neurological Therapeutics
DOI： 10.15082/jsnt.36.5_584 　

ISSN： 0916-8443

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<p>Motor neuron diseases (MND) are devastating neurodegenerative disorder which primary affects motor neurons. Amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), and spinal bulbar muscular atrophy (SBMA) are representative MND. Since the advent of novel drugs of SMA (Nusinersen) and SBMA (Leuprorelin) in 2017, the treatment of MND has changed dramatically and the door of new hope has opened. This review provides an overview of preclinical and clinical advances in MND research, future issues and prospects, and summarizes selected key literature on therapeutic approaches in 2018.</p>
Modeling sporadic ALS in iPSC-derived motor neurons identifies a potential therapeutic agent International-journal Peer-reviewed

Koki Fujimori, Mitsuru Ishikawa, Asako Otomo, Naoki Atsuta, Ryoichi Nakamura, Tetsuya Akiyama, Shinji Hadano, Masashi Aoki, Hideyuki Saya, Gen Sobue, Hideyuki Okano

Nature Medicine　24　(10)　1579-1589　2018/10/01

DOI： 10.1038/s41591-018-0140-5 　

ISSN： 1078-8956

eISSN： 1546-170X
Antagonizing bone morphogenetic protein 4 attenuates disease progression in a rat model of amyotrophic lateral sclerosis International-journal Peer-reviewed

Tomomi Shijo, Hitoshi Warita, Naoki Suzuki, Kensuke Ikeda, Shio Mitsuzawa, Tetsuya Akiyama, Hiroya Ono, Ayumi Nishiyama, Rumiko Izumi, Yasuo Kitajima, Masashi Aoki

Experimental Neurology　307　164-179　2018/09

DOI： 10.1016/j.expneurol.2018.06.009 　

ISSN： 0014-4886

eISSN： 1090-2430
TARDBP p.G376D mutation, found in rapid progressive familial ALS, induces mislocalization of TDP-43 International-journal Peer-reviewed

Shio Mitsuzawa, Tetsuya Akiyama, Ayumi Nishiyama, Naoki Suzuki, Masaaki Kato, Hitoshi Warita, Rumiko Izumi, Shion Osana, Shingo Koyama, Takeo Kato, Yoshihiro Suzuki, Masashi Aoki

eNeurologicalSci　11　20-22　2018/06

DOI： 10.1016/j.ensci.2018.04.001 　

eISSN： 2405-6502
Comprehensive targeted next-generation sequencing in Japanese familial amyotrophic lateral sclerosis International-journal Peer-reviewed

Ayumi Nishiyama, Tetsuya Niihori, Hitoshi Warita, Rumiko Izumi, Tetsuya Akiyama, Masaaki Kato, Naoki Suzuki, Yoko Aoki, Masashi Aoki

Neurobiology of Aging　53　194.e1-194.e8　2017/05/01

DOI： 10.1016/j.neurobiolaging.2017.01.004 　

ISSN： 0197-4580

eISSN： 1558-1497
Prominent sensory involvement in a case of familial amyotrophic lateral sclerosis carrying the L8V SOD1 mutation International-journal Peer-reviewed

Ayumi Nishiyama, Hitoshi Warita, Toshiaki Takahashi, Naoki Suzuki, Shuhei Nishiyama, Ohito Tano, Tetsuya Akiyama, Yasuaki Watanabe, Kenta Takahashi, Hiroshi Kuroda, Masaaki Kato, Maki Tateyama, Tetsuya Niihori, Yoko Aoki, Masashi Aoki

Clinical Neurology and Neurosurgery　150　194-196　2016/11/01

DOI： 10.1016/j.clineuro.2016.08.008 　

ISSN： 0303-8467

eISSN： 1872-6968
Genotype–phenotype relationships in familial amyotrophic lateral sclerosis with FUS/TLS mutations in Japan International-journal Peer-reviewed

Tetsuya Akiyama, Hitoshi Warita, Masaaki Kato, Ayumi Nishiyama, Rumiko Izumi, Chikako Ikeda, Masaki Kamada, Naoki Suzuki, Masashi Aoki

Muscle and Nerve　54　(3)　398-404　2016/09/01

DOI： 10.1002/mus.25061 　

ISSN： 0148-639X

eISSN： 1097-4598
Establishment of in Vitro FUS-Associated Familial Amyotrophic Lateral Sclerosis Model Using Human Induced Pluripotent Stem Cells International-journal Peer-reviewed

Naoki Ichiyanagi, Koki Fujimori, Masato Yano, Chikako Ishihara-Fujisaki, Takefumi Sone, Tetsuya Akiyama, Yohei Okada, Wado Akamatsu, Takuya Matsumoto, Mitsuru Ishikawa, Yoshinori Nishimoto, Yasuharu Ishihara, Tetsushi Sakuma, Takashi Yamamoto, Hitomi Tsuiji, Naoki Suzuki, Hitoshi Warita, Masashi Aoki, Hideyuki Okano

Stem Cell Reports　6　(4)　496-510　2016/04

DOI： 10.1016/j.stemcr.2016.02.011 　

ISSN： 2213-6711
FALS with FUS mutation in Japan, with early onset, rapid progress and basophilic inclusion (Journal of Human Genetics (2015) 60, 653-654) International-journal Peer-reviewed

Naoki Suzuki, Masashi Aoki, Hitoshi Warita, Masaaki Kato, Hideki Mizuno, Naoko Shimakura, Tetsuya Akiyama, Hirokazu Furuya, Toshihiro Hokonohara, Akiko Iwaki, Shinji Togashi, Hidehiko Konno, Yasuto Itoyama

Journal of Human Genetics　60　(10)　653-654　2015/10/01

DOI： 10.1038/jhg.2015.93 　

ISSN： 1434-5161

eISSN： 1435-232X
体性感覚前兆の診断にビデオ脳波モニタリングが有用であった左中心溝底部皮質形成異常の1例 Peer-reviewed

秋山徹也, 神一敬, 柿坂庸介, 加藤量広, 藤川真由, 岩崎真樹, 青木正志, 中里信和

臨床神経学　54　(11)　929-929　2014/11
Publisher: (一社)日本神経学会
ISSN： 0009-918X

eISSN： 1882-0654
疣贅塞栓による多発脳梗塞を合併し、単核球優位の髄液細胞増多を認めた感染性心内膜炎の1例

千葉哲矢, 突田健一, 光澤志緒, 秋山徹也, 渡辺源也, 成川孝一, 佐藤大樹, 高橋悟朗, 鈴木博義, 鈴木靖士

神経治療学　31　(5)　629-629　2014/09
Publisher: (一社)日本神経治療学会
ISSN： 0916-8443

eISSN： 2189-7824
Neuronal representation of task performance in the medial frontal cortex undergoes dynamic alterations dependent upon the demand for volitional control of action Peer-reviewed

Yoshiya Matsuzaka, Tetsuya Akiyama, Hajime Mushiake

Experimental Brain Research　229　(3)　395-405　2013/09

DOI： 10.1007/s00221-013-3454-z 　

ISSN： 0014-4819

eISSN： 1432-1106
Participation of neurons in multiple sectors of medial frontal cortex undergoes dynamic alterations depending on the demand for volitional control of action Peer-reviewed

Yoshiya Matsuzaka, Tetsuya Akiyama, Hajime Mushiake

Experimental Brain Res.　2013

DOI： 10.1007/s00221-013-3454-z 　
Neuronal activity in the primate dorsomedial prefrontal cortex contributes to strategic selection of response tactics Peer-reviewed

Yoshiya Matsuzaka, Tetsuya Akiyama, Jun Tanji, Hajime Mushiake

Proceedings of the National Academy of Sciences of the United States of America　109　(12)　4633-4638　2012/03/20

DOI： 10.1073/pnas.1119971109 　

ISSN： 0027-8424

eISSN： 1091-6490
Continuous administration of poloxamer 188 reduces overload-induced muscular atrophy in dysferlin-deficient SJL mice International-journal Peer-reviewed

Naoki Suzuki, Tetsuya Akiyama, Toshiaki Takahashi, Hazuki Komuro, Hitoshi Warita, Maki Tateyama, Yasuto Itoyama, Masashi Aoki

Neuroscience Research　72　(2)　181-186　2012/02

DOI： 10.1016/j.neures.2011.10.005 　

ISSN： 0168-0102

eISSN： 1872-8111
若年発症・急速進行・好塩基性封入体を特徴としFUS遺伝子変異を伴う家族性ALSの5家系

青木正志, 鈴木直輝, 割田仁, 加藤昌昭, 水野秀紀, 島倉奈緒子, 秋山徹也, 今野秀彦, 糸山泰人

臨床神経学　50　(12)　1084-1084　2010/12
Publisher: (一社)日本神経学会
ISSN： 0009-918X

eISSN： 1882-0654
FALS with FUS mutation in Japan, with early onset, rapid progress and basophilic inclusion International-journal Peer-reviewed

Naoki Suzuki, Masashi Aoki, Hitoshi Warita, Masaaki Kato, Hideki Mizuno, Naoko Shimakura, Tetsuya Akiyama, Hirokazu Furuya, Toshihiro Hokonohara, Akiko Iwaki, Shinji Togashi, Hidehiko Konno, Yasuto Itoyama

Journal of Human Genetics　55　(4)　252-254　2010/04

DOI： 10.1038/jhg.2010.16 　

ISSN： 1434-5161

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Misc. 20

ALS関連RNA結合タンパク質の機能喪失が収束するUNC13A発現制御異常の分子機構

渡辺靖章, 渡辺靖章, 鈴木直輝, 鈴木直輝, 中川直, 中川直, 細金正樹, 秋山徹也, 森本悟, 森本悟, 岡野栄之, 岡野栄之, 青木正志, 中山啓子, 中山啓子

日本分子生物学会年会プログラム・要旨集(Web)　48th　2025
細胞膜修復機構に着目したdysferlin異常症の病態解明と治療法開発

小野洋也, 鈴木直輝, 菅野新一郎, 川原玄理, 井泉瑠美子, 高橋俊明, 北嶋康雄, 長名シオン, 秋山徹也, 池田謙輔, 四條友望, 光澤志緒, 割田仁, 永富良一, 荒木伸一, 安井明, 林由起子, 三宅克也, 青木正志

日本筋学会学術集会プログラム・抄録集　4回　160-160　2018/08
Publisher: 日本筋学会
ISSN： 2433-975X
細胞膜修復機構に着目したdysferlin異常症の病態解明と治療法開発

小野洋也, 小野洋也, 鈴木直輝, 菅野新一郎, 川原玄理, 井泉瑠美子, 高橋俊明, 北嶋康雄, 長名シオン, 秋山徹也, 池田謙輔, 四條友望, 光澤志緒, 割田仁, 永富良一, 荒木伸一, 安井明, 林由起子, 三宅克也, 三宅克也, 青木正志

日本筋学会学術集会プログラム・抄録集　4th　160-160　2018/08/01
Publisher: 日本筋学会
ISSN： 2433-975X
筋萎縮性側索硬化症モデル脊髄のアストロサイトにおける骨形成蛋白質の過剰発現

四條友望, 割田仁, 鈴木直輝, 池田謙輔, 小野洋也, 秋山徹也, 光澤志緒, 西山亜由美, 井泉瑠美子, 青木正志

日本再生医療学会総会(Web)　17th　2018
運動ニューロン疾患の治療の進歩 Invited

秋山徹也

神経治療学　35　(5)　609-613　2018
細胞膜修復機構に着目したジスフェルリン異常症の病態解明と治療法開発

小野洋也, 鈴木直輝, 菅野新一郎, 川原玄理, 井泉瑠美子, 高橋俊明, 北嶋康雄, 長名シオン, 秋山徹也, 池田謙輔, 四條友望, 光澤志緒, 割田仁, 永富良一, 荒木伸一, 安井明, 林由起子, 三宅克也, 三宅克也, 青木正志

筋ジストロフィー医療研究　4　87-87　2017/10
Publisher: 筋ジストロフィー医療研究会
ISSN： 2433-1708
細胞膜修復機構に着目したDysferlinopathyの病態解明と治療法開発

小野洋也, 鈴木直輝, 菅野新一郎, 川原玄理, 井泉瑠美子, 高橋俊明, 北嶋康雄, 長名シオン, 秋山徹也, 池田謙輔, 四條友望, 光澤志緒, 割田仁, 永富良一, 荒木伸一, 安井明, 林由起子, 三宅克也, 青木正志

日本筋学会学術集会プログラム・抄録集　3回　141-141　2017/07
Publisher: 日本筋学会
ISSN： 2433-975X
細胞膜修復機構に着目したDysferlinopathyの病態解明と治療法開発

小野洋也, 鈴木直輝, 菅野新一郎, 川原玄理, 井泉瑠美子, 高橋俊明, 北嶋康雄, 長名シオン, 秋山徹也, 池田謙輔, 四條友望, 光澤志緒, 割田仁, 永富良一, 荒木伸一, 安井明, 林由起子, 三宅克也, 三宅克也, 青木正志

日本筋学会学術集会プログラム・抄録集　3回　141-141　2017/07
Publisher: 日本筋学会
ISSN： 2433-975X
マイクロ流体デバイスを用いた運動ニューロンの軸索病態の解析

鈴木直輝, 秋山徹也, 川田治良, 川田治良, 舟山亮, 岡野栄之, 中山啓子, 藤井輝夫, 青木正志

日本細胞生物学会大会(Web)　69回　25-25　2017/05
Publisher: (一社)日本細胞生物学会
筋萎縮性側索硬化症ラットモデル脊髄における内在性再生機転

割田仁, 四條友望, 池田謙輔, 小野洋也, 秋山徹也, 光澤志緒, 西山亜由美, 井泉瑠美子, 鈴木直輝, 青木正志

再生医療　16　436　2017/02/01

ISSN： 1347-7919
筋萎縮性側索硬化症モデルラットにおけるコンドロイチン硫酸プロテオグリカン受容体の異所性発現

四條友望, 割田仁, 鈴木直輝, 池田謙輔, 秋山徹也, 小野洋也, 光澤志緒, 西山亜由美, 井泉瑠美子, 青木正志

再生医療　16　435　2017/02/01

ISSN： 1347-7919
神経変性疾患領域における基盤的調査研究家族性ALSにおける遺伝子解析

青木正志, 鈴木直輝, 加藤昌昭, 割田仁, 井泉瑠美子, 西山亜由美, 秋山徹也, 島倉奈緒子

神経変性疾患領域における基盤的調査研究平成27年度総括・分担研究報告書　66‐67　2016
日本のFUS/TLS遺伝子関連家族性ALS症例における遺伝子型-表現型相関(Genotype-phenotype correlation with FUS/TLS-linked familial ALS cases in Japan)

秋山徹也, 鈴木直輝, 割田仁, 加藤昌昭, 西山亜由美, 井泉瑠美子, 池田謙輔, 小野洋也, 四條友望, 青木正志

臨床神経学　55　(Suppl.)　S237-S237　2015/12
Publisher: (一社)日本神経学会
ISSN： 0009-918X

eISSN： 1882-0654
運動ニューロン変性モデルラット脊髄微小血管のペリサイト新生

割田仁, 四條友望, 池田謙輔, 小野洋也, 秋山徹也, 鈴木直輝, 加藤昌昭, 青木正志

再生医療　14　336　2015/02/01

ISSN： 1347-7919
アルコール性てんかんを当初疑った脳静脈洞血栓症の1例

秋山徹也, 向井由幸, 小野紘彦, 黒田宙, 武田篤, 青木正志

臨床神経学　54　(3)　244-244　2014/03
Publisher: (一社)日本神経学会
ISSN： 0009-918X
日本における封入体筋炎の臨床・病理学的特徴の検討

鈴木直輝, 青木正志, 竪山真規, 割田仁, 井泉瑠美子, 秋山徹也, 新井法子, 糸山泰人, 森まどか, 日下博文, 樋口逸郎, 近藤智善, 内野誠, 梶龍兒, 西野一三

臨床神経学　50　(12)　1137-1137　2010/12
Publisher: (一社)日本神経学会
ISSN： 0009-918X
神経変性疾患に関する調査研究若年発症・急速進行・好塩基性封入体を特徴としFUS遺伝子に変異を伴う日本人家族性筋萎縮性側索硬化症の5家系

青木正志, 鈴木直輝, 割田仁, 加藤昌昭, 水野秀紀, 島倉奈緒子, 秋山徹也, 古谷博和, 鉾之原敏博, 岩城明子, 服巻保幸, 富樫慎二, 今野秀彦, 糸山泰人

神経変性疾患に関する調査研究平成21年度総括・分担研究報告書　55-57　2010
日本における封入体筋炎の臨床・病理学的特徴の検討

鈴木直輝, 青木正志, 竪山真規, 割田仁, 井泉瑠美子, 秋山徹也, 新井法子, 糸山泰人, 森まどか, 日下博文, 樋口逸郎, 近藤智善, 内野誠, 梶龍兒, 西野一三

日本神経学会総会プログラム・抄録集　51st　234　2010
若年発症・急速進行・好塩基性封入体を特徴としFUS遺伝子変異を伴う家族性ALSの5家系

青木正志, 鈴木直輝, 割田仁, 加藤昌昭, 水野秀紀, 島倉奈緒子, 秋山徹也, 今野秀彦, 糸山泰人

日本神経学会総会プログラム・抄録集　51st　179　2010
若年発症・急速進行・好塩基性封入体を特徴としFUS/TLSに変異を持つ日本人家族性筋萎縮性側索硬化症の3家系

鈴木直輝, 青木正志, 割田仁, 加藤昌昭, 水野秀紀, 島倉奈緒子, 秋山徹也, 古谷博和, 鉾之原敏博, 岩城明子, 服巻保幸, 富樫慎二, 今野秀彦, 糸山泰人

日本人類遺伝学会大会プログラム・抄録集　54th　200　2009

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Books and Other Publications 2

神経内科Clinical Questions ＆ Pearls

秋山徹也

中外医学社　2017
神経症候群(第2版)-その他の神経疾患を含めて-.

秋山徹也

日本臨牀　2014

Presentations 4

マイクロ流体デバイスで切り拓く運動ニューロン疾患研究 Invited

秋山徹也, 鈴木直輝

第48回日本神経組織培養研究会　2025/11/24
IDENTIFICATION OF KIF5A AS A KEY FACTOR LINKING AXONAL PATHOLOGY IN SMA AND ALS

Tetsuya Akiyama

Annual SMA Research & Clinical Care Meeting, 2025　2025/06/25
Elucidating axonal pathophysiology of fused in sarcoma (FUS)-mutant amyotrophic lateral sclerosis (ALS) using human-induced pluripotent stem cells (hiPSCs)-derived motor neurons.

2019/07/25
ELUCIDATING AXONAL PATHOPHYSIOLOGY OF IPSCS-DERIVED MOTOR NEURONS FROM FUSED IN SARCOMA (FUS)- ALS PATIENT

Tetsuya Akiyama, Naoki Suzuki, Mitsuru Ishikawa, Fumiyoshi Fujishima, Jiro Kawada, Teruo Fujii, Ryo Funayama, Keiko Nakayama, Hiroaki Mitsuhashi, Hitoshi Warita, Hideyuki Okano, Masashi Aoki

ISSCR 2019　2019/06/28

Research Projects 7

ALS軸索におけるRNA・タンパク質ネットワーク破綻の分子基盤解明と治療応用

青木正志, 鈴木直輝, 秋山徹也

Offer Organization: 日本学術振興会

System: 科学研究費助成事業

Category: 基盤研究(A)

Institution: 東北大学

2026/04/01 - 2030/03/31
Defining axonal mechanisms and therapeutic potential of KIF5A in spinal muscular atrophy

Offer Organization: Cure SMA Scientific Advisory Board (SAB) https://www.curesma.org/cure-sma-awards-150000-grant-to-tetsuya-akiyama-md-phd-stanford-university-school-of-medicine/

Institution: https://www.curesma.org/cure-sma-awards-150000-grant-to-tetsuya-akiyama-md-phd-stanford-university-school-of-medicine/

2026/04 - 2028/03
Therapeutic and mechanistic dissection of KIF5A regulation in SMA

Aaron Gitler, Tetsuya Akiyama

Offer Organization: SMA foundation

Institution: Stanford University

2025/12 - 2027/12
Defining the role of KIF5A in SMA

Aaron D Gitler, Tetsuya Akiyama

Offer Organization: SMA foundation

Institution: Stanford University

2024/12 - 2025/12
Screening therapeutic targets for nuclear-cytoplasmic shuttling in age-related neurodegenerative diseases ALS and FTD

Offer Organization: Stanford University

System: Stanford Training Program in Aging Research

2021/04 - 2025/04
Neurodegenerative disorder including ALS and Parkinson's disease.

Institution: Stanford University

2020/09 - 2024/09
FUS遺伝子変異を伴う筋萎縮性側索硬化症の軸索形態に注目した病態解明 Competitive

秋山徹也

Offer Organization: 学術研究助成基金助成金

System: 若手研究

Category: 若手研究

Institution: 東北大学

2019/04 - 2022/03

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原因遺伝子変異が明らかとなっている家族性ALSは病態解明のために重要である。申請者はfused in sarcoma（FUS）が日本人の家族性ALSの原因遺伝子の2番目に多いことを見出し注目してきた。FUSはRNA結合能を介した軸索での物質輸送や局所翻訳を担っており、軸索病態に注目する上でFUSに注目することは重要である。そこで、FUSに変異を持つ家族性ALS患者よりiPS細胞を樹立し、病態解析を行い、ALS患者由来運動ニューロンにおいては軸索の分岐が増えているという新規細胞表現型を同定した。さらに、FUS変異を有する運動ニューロンで軸索の分岐が増える機序を解明するため、FUSがRNA代謝に関わることに注目し、軸索のRNAの変動を網羅的に解析した。軸索のみを回収するため、目視でも確認可能な軸索の束を作成できるマイクロ流体デバイスとRNAシーケンスを組み合わせて軸索のRNA変動を解析し、軸索形態異常に関連する因子としてFos-Bを同定した。Fos-Bを人工的に発現させると、健常なiPS細胞由来の運動ニューロンだけでなく、ゼブラフィッシュの運動ニューロン軸索も異常に分岐することから、生体内におけるFos-Bの機能の重要性も示した。またFos-Bの抑制により、FUS変異を有する運動ニューロン軸索の形態を改善できることを示し、新規治療標的としての可能性を見出し、論文として報告（EBioMedicine 2019）、また、国内外の学会で成果報告・研究発展について議論した（ISCCR , 日本神経科学大会, 日本神経学会学術集会）。

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