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N e w s our recent activities

2025/5/26 NEW MEETING We gave presentations and organized a symposium in 66th Annual Meeting of the Japanese Society of Neurology (Osaka, May 21-24):

Prof. Yamanaka co-organized the symposium entitled "Computational Neurology: understanding neurodegenerative diseases through mathematics and omics" with Assoc. Prof. Yuichiro Yada (Nagoya Univ).

Stmposist:
Dr. Komine (in the above symposium)
Dr. Endo (in the Late Breaking Symposium organized by Prof. Kazuma Saigo (Kindai University) and Assoc. Prof. Tatsusada Okuno (Osaka Univ))
Poster Presentation: Mr. Sugihara

Mr. Sugihara and Prof. Yamanaka in the poster presentation area

2025/5/8 NEW RESEARCH Our Review Work is now open in Bioessays:

　In this review, we discussed a hypothesis that disruption of mitochondria-associated membrane (MAM) induces neurodegenerative diseases via deregulation of cellular proteostasis.

Open Access
Watanabe S, Yamanaka K
Mitochondria and Endoplasmic Reticulum Contact Site as a Regulator of Proteostatic Stress Responses in Neurodegenerative Diseases
Bioessays 4: e70016, 2025.

2025/5/8 NEW RESEARCH Our work is now open in Scientific Reports:

　This study focused on the impact of male sex hormone (androgens) on the pathology of Alzheimer's disease (AD). We found that expression levels of androgen receptor (AR/Ar) were significantly decreased in the brains of male patients with early AD pathology and in isolated microglia of male AD model mice (App^{NL-G-F/NL-G-F} mice). Long-term systemic androgen deprivation by castration altered the expression levels of neuroinflammation-related genes in isolated microglia of male App^{NL-G-F/NL-G-F} mice. These results suggest that androgens may influence neuroinflammation in AD.

Open Access
Maekawa K, Sobue A, Komine O, Saito Y, Murayama S, Saido TC, Saito T, Yamanaka K
Long-term systemic androgen deprivation partially modulates neuroinflammation in male App^{NL-G-F/NL-G-F} mice
Scientific Reports 15: 14702, 2025.

2025/5/1 NEW Dr. Kotaro Oiwa moved to Salk Institute for Biological Studies as a postdoctoral fellow.

2023/4/1 NEW Mrs. Keigo Hashiba (D1) and Koki Watanabe (M1) joined our lab. Dr. Horiuchi and Ms. Maekawa became Assistant Professors.

Our group photo in Apr. 2025

2025/4/1 NEW Dr. Atushi Shimohata moved to Technical Center of Nagoya University as a technical staff.

2025/4/1 NEW GRANT We are selected for Grant-in-Aid for Scientific Research in 2025 as follows:

Dr. Yamanaka: Grant-in-Aid for Scientific Research (A) (continuing)
Dr. Komine: Grant-in-Aid for Scientific Research (C) (continuing)
Dr. Watanabe: Grant-in-Aid for Scientific Research (C) (continuing)
Dr. Endo: Grant-in-Aid for Scientific Research (C) (continuing)
Dr. Kawade: Grant-in-Aid for Early-Career Scientists (continuing)
Dr. Shinno: Grant-in-Aid for Research Activity Start-up (new)
Dr. Oiwa: Grant-in-Aid for Research Activity Start-up (continuing), Grant-in-Aid for Early-Career Scientists (new)

Also, we are selected for
AMED　(Multidisciplinary Frontier Brain and Neuroscience Discoveries) (collaboration)
AMED-GAPFREE (collaboration)
JST Fusion Oriented REsearch for disruptive Science and Technology (Dr. Endo)
JST MOONSHOT R&D program (Performer)

2025/3/25 NEW AWARD Dr. Mai Horiuchi was awarded a Ph.D. in Medicine.

Prof. Yamanaka and Dr. Horiuchi in our lab

Her thesis is the following article published in Acta Neuropathologica Communications, which revealed that excess TDP-43 in oligodendrocytes induces motor deficits in mice.

Open Access
Horiuchi M, Watanabe S, Komine O, Takahashi E, Kaneko K, Itohara S, Shimada M, Ogi T, Yamanaka K
ALS-linked mutant TDP-43 in oligodendrocytes induces oligodendrocyte damage and exacerbates motor dysfunction in mice
Acta Neuropathologica Communications 12: 184, 2024.

Press release from Nagoya Univ

2025/2/21 NEW AWARD Ms. Noda won a Most Excellent Networking Award in 17th NAGOYA Global Retreat (6th CIBoG Retreat).

Prof. Yamanaka and Ms. Noda in our lab

2025/1/1 NEW Dr. Akira Sobue moved to Nagoya City University as an assistant professor (Department of Clinical Pharmaceutics, Graduate School of Medical Sciences).

He still joins us as a collaborative researcher.

2024/12/10 RESEARCH Our paper is now open in Acta Neuropathologica Communications :

　Our study identified that overexpression of TDP-43, a product of ALS-causative gene, in oligodendrocytes induced oligodendrocyte dysfunction and motor dysfunction in mice. Further research focused on oligodendrocytes holds the potential to develop a new therapeutic strategy for ALS.

Open Access
Horiuchi M, Watanabe S, Komine O, Takahashi E, Kaneko K, Itohara S, Shimada M, Ogi T, Yamanaka K
ALS-linked mutant TDP-43 in oligodendrocytes induces oligodendrocyte damage and exacerbates motor dysfunction in mice
Acta Neuropathologica Communications 12: 184, 2024.

Press release from Nagoya Univ

2024/11/27 RESEARCH Our paper is now open in Cell Death & Disease :

Our study identified that cannabinoid receptor type II (CB2) is involved in Alzheimer's disease (AD) progression and is commonly upregulated in the human AD brain and microglia isolated from App^{NL-G-F/NL-G-F} mice. Chronic oral administration of JWH 133, a selective CB2 agonist, significantly ameliorated the cognitive impairment and neuroinflammation in App^{NL-G-F/NL-G-F} mice. Therefore, our study has implications that CB2 may represent an attractive therapeutic target for the treatment of AD and perhaps other neurodegenerative diseases involving neuroinflammation.

Open Access
Sobue A, Komine O, Endo F, Kakimi C, Miyoshi Y, Kawade N, Watanabe S, Saito Y, Murayama S, Saido SC, Saito T, Yamanaka K
Microglial cannabinoid receptor type II stimulation improves cognitive impairment and neuroinflammation in Alzheimer’s disease mice by controlling astrocyte activation
Cell Death & Disease 15: 858, 2024.

2024/11/27 MEETING Drs. Komine, Kawade, Sobue, and Ms. Maekawa gave poster presentations in The 43rd Annual Meeting of Japan Society for Dementia Research (Fukushima, Nov. 21-23).

2024/11/10 MEETING Prof. Yamanaka & Mr. Sakai gave presentations in The 97th Annual Meeting of the Japanese Biochemical Society (Yokohama, Nov. 6-8).

Symposist: Dr. Yamanaka (in the symposium entitled "Biochemistry of Rare and Intractable Diseases: Toward the Realization of Medicine that Leaves No One Behind" organized by Drs. Motoi Kanagawa (Ehime Univ) & Yoshitugu Aoki (The National Center of Neurology and Psychiatry))
Poster presentation: Mr. Sakai

2024/10/1 Mrs. Keito Sano & Hideki Yamawaki joined our lab in Training for Medical Research.

2024/9/1 Dr. Ting Wang moved to Jilin University as a postdoctoral fellow.

2024/8/1 GRANT Drs. Oiwa and Shinno were selected for Grant-in-Aid for Research Activity Start-up, respectively.

2024/7/24 AWARD Drs. Endo and Oiwa won the Japan Neuroscience Society Young Investigator Award (to Dr. Endo) and Toshihiko Tokizane Memorial Award for Excellent Graduate Study in Neuroscience (to Dr. Oiwa) in Neuro2024, respectively.

At the celemony. Professor Dr. Masahisa Katsuno (Grad Sch Med, Nagoya Univ), Dr. Endo, Dr. Oiwa and Professor Dr. Yamanaka from the left.

2024/8/1 MEETING We gave presentations and organized a symposium in Neuro2024 (Joint Congress of the 47th Annual Meeting of Japan Neuroscience Society, the 57th Annual Meeting of the Japanese Society for Neurochemistry, the 46th Annual Meeting of the Japanese Society of Biological Psychiatry, and the 8th FAONS Congress).

Dr. Oiwa co-organized the symposium "Frontiers of ALS/FTD Research by Young Researchers" with Dr. Yuka Koike (Niigata Univ).
Drs. Yamanaka and Watanabe chaired the oral presentations, respectively.

Symposist: Dr. Oiwa (organizer)
Training session for early-career scientists: Mr. Sakai
Oral presentations: Dr. Endo, Dr. Shinno
Poster presentations: Dr. Komine, Dr. Watanabe, Dr. Kawade, Dr. Sobue, Dr. Shimohata, Dr. Wang, Ms. Maekawa, Dr. Horiuchi

2024/6/23 AWARD Dr. Ting Wang was awarded Ph.D. in Medicine.

In our lab. Professor Dr. Yamanaka & Dr. Wang.

Her thesis is based on the following article published in the Journal of Neuroinflammation, which revealed that dimethyl fumarate activates the oxidative stress response in astrocytes to improve AD pathology.

Open Access
Wang T, Sobue A, Watanabe S, Komine O, Saido TC, Saito T, Yamanaka K
Dimethyl fumarate improves cognitive impairment and neuroinflammation in mice with Alzheimer’s disease.
Journal of Neuroinflammation 21(1): 55, 2023.

2024/5/1 NEW RESEARCH Our collaborative work with Liverpool Univ is now open in Scientific Reports:

In this study, we revealed that ebselen derivatives delayed the onset of SOD1-linked ALS model mice, which may contribute future therapy for SOD1-linked familial ALS.

Open Access
Watanabe S, Amporndanai K, Awais R, Latham C, Awais M, O'Neill PM, Yamanaka K, Hasnain S
Ebselen analogues delay disease onset and its course in fALS by on-target SOD-1 engagement.
Scientific Reports 14: 12118, 2024.

2024/4/1 Professor Dr. Yamanaka has been appointed Vince President (Research) of Nagoya Univ.

2024/4/1 RESEARCH Our work is now open in Journal of Neuroinflammation:

In this study, we found that dimethyl fumarate, a therapeutic agent for multiple sclerosis, activates the transcription factor NF-E2-related factor 2 (Nrf2) in astrocytes, a type of glial cell, to improve neuroinflammation and cognitive function in a mouse model of Alzheimer's disease (App^{NL-G-F/NL-G-F}), which may lead to the development of novel Alzheimer's disease treatment and prevention methods targeting Nrf2 in the future.

Open Access
Wang T, Sobue A, Watanabe S, Komine O, Saido TC, Saito T, Yamanaka K
Dimethyl fumarate improves cognitive impairment and neuroinflammation in mice with Alzheimer’s disease.
Journal of Neuroinflammation 21(1): 55, 2023.

2024/4/1 GRANT We are selected for Grant-in-Aid for Scientific Research in 2024 as follows:

Dr. Yamanaka: Grant-in-Aid for Scientific Research (A) (continuing)
Dr. Komine: Grant-in-Aid for Scientific Research (C) (new)
Dr. Watanabe: Grant-in-Aid for Scientific Research (C) (continuing)
Dr. Sobue: Grant-in-Aid for Early-Career Scientists (continuing)
Dr. Kawade: Grant-in-Aid for Early-Career Scientists (continuing)
Dr. Endo: Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Transformative Research Areas (A) (continuing)
Dr. Shimohata: Grant-in-Aid for Early-Career Scientists (new)

Also, we are selected for
AMED-LEAP (collaboration)
AMED（Project for Elucidation of Mechanisms of Psychiatric and Neurological Diseases）
JST MOONSHOT R&D program (Performer)

2024/3/25 AWARD Dr. Kei Hashimoto and Ms. Sara Yanagisawa were awarded Ph.D. in Medicine and Master's degree in Medical Sciences, respectively.

In our lab. Ms. Yanagisawa, Professor Dr. Yamanaka, and Dr. Hashimoto from the left.

Thesis of Dr. Hashimoto is based on his findings published in the Journal of Biological Chemistry, which revealed the existence of a canine-specific vulnerability mechanism in SOD1, the protein responsible for canine degenerative myelopathy.

Open Access
Hashimoto K, Watanabe S, Akutu M, Mukai N, Kamishina H, Furukawa Y, Yamanaka K
Intrinsic structural vulnerability in the hydrophobic core induces species-specific aggregation of canine SOD1 with degenerative myelopathy–linked E40K mutation.
Journal of Biological Chemistry 299(6): 104798, 2023.

2024/2/28 Professor Dr. Yamanaka gave a lecture in the Tokyo Medical & Dental University.

2024/2/8 Professor Dr. Yamanaka gave a lecture in the Niigata University.

2024/2/6 AWARD Dr. Oiwa was awarded Ph.D. in Medicine.

His thesis is based on the following article publised in Science Advances, which demonstrates that TDP-43 monomerization is a key abnormality that causes TDP-43 pathology in ALS.

Open Access
Oiwa K, Watanabe S, Onodera K, Iguchi Y, Kinoshita Y, Komine O, Sobue A, Okada Y, Katsuno M, Yamanaka K
Monomerization of TDP-43 is a key determinant for inducing TDP-43 pathology in amyotrophic lateral sclerosis.
Science Advances 9(31): eadf6895, 2023.

Press release from Nagoya Univ

2024/2/1 RESEARCH Our work is now open in iScience:

　Genetic background variation impacts microglial heterogeneity, especially disease-associated microglia (DAM), to affect the disease progression in ALS. In a Balb strain, neuroprotective DAM was less induced than a B6(J) strain, resulting in reduced production of insulin-like growth factor-1 (IGF-1) and macrophage colony-stimulating factor (M-CSF). Targeting the reactivity of microglia may be a future therapeutic stratgey for ALS.

Open Access
Komine O, Ohnuma S, Hinohara K, Hara Y, Shimada M, Akashi T, Watanabe S, Sobue A, Kawade N, Ogi T, Yamanaka K
Genetic background variation impacts microglial heterogeneity and disease progression in amyotrophic lateral sclerosis model mice.
iScience 27(2): 108872, 2024.

Press release from Nagoya Univ

2024/2/1 MEETING Professor Dr. Yamanaka gave a special invited lecture in the 1st International Conference on Neuroscience & Osetoimmunology (Nagano).

2024/1/25 MEETING Dr. Komine gave a invited presentation in the semminer of Mathmatical Sciences.

2023/12/7 MEETING We gave presentations in the fllowing meetings and symposiums:

34th International Symposium on ALS/MND (Basel, Sqitzland): Poster presentation (Dr. Watanabe)
The 46th Anuual Meeting of the Japanese Association of Neural Tissue Culture (Miura, Kanagawa Pref.): Special invited talk entitled "Molecular basis of TDP-43 pathology in ALS." (Dr. Yamanaka)
The 35th Annual Meeting of the Japanese Society for Neuroimmunology (Tokyo International Forum): Symposist (Dr. Yamanaka)
The 7th ALS Cafe (Toho Univ, online): Invited talk (Dr. Yamanaka)

2023/11/27 MEETING Dr. Komine, Dr. Kawade, and Ms. Maekawa gave poster presentations in the 42nd Annual Meeting of Japan Society for Dementia Research (Nara Convention Center).

2023/11/16 RESEARCH Our work is now open in Proceedings of the National Academy of Sciences, USA:

　We found that disruption of the mitochondria-associated membranes (MAMs) in Amyotrophic Lateral Sclerosis (ALS) iactivates TANK-binding kinase 1 (TBK1), one of the ALS causative gene products. The TBK1 inactivation resulted in impaired cellular stress response leading to cell death in vitro and motor dysfunction in vivo. Thus, MAM-TBK1 axis may be a promising target for a future ALS therapy.

Open Access
Watanabe S, Murata Y, Oka Y, Oiwa K, Horiuchi M, Iguchi Y, Komine O, Sobue A, Okada Y, Katsuno M, Ogi T, Yamanaka K
Mitochondria-associated membrane collapse impairs TBK1-mediated proteostatic stress response in ALS.
Proceedings of the National Academy of Sciences, USA 120(47): e2315347120, 2024.

Press release from Nagoya Univ

2023/10/19 Our work (Oiwa et al. Sci Adv 2023) were introduced in NHK (Japan Broadcasting Corporation).

2023/10/1 Mr. Shunsuke Yokoi and Ms. Ayumi Matsui have joined to our lab.

2023/8/4 RESEARCH Our work is now open in Science Advances:

We found that TDP-43 dimerization/multimerization is impaired in the postmortem brains and spinal cords of patients with sporadic amyotrophic lateral sclerosis (ALS). Expression of N-terminal dimerization-deficient mutant TDP-43 in Neuro2a cells and induced pluripotent stem cell-derived motor neurons recapitulates TDP-43 pathology. Moreover, TDP-DiLuc, a novel reporter assay to evaluate TDP-43 dimerization/multimerization, could detect decreased N-terminal dimerization of TDP-43 prior to the TDP-43 pathological changes. Our findings may be important in future research on early pathogenic events related to TDP-43 and in the search for early diagnostic markers or therapeutic strategies for ALS.

Open Access
Oiwa K, Watanabe S, Onodera K, Iguchi Y, Kinoshita Y, Komine O, Sobue A, Okada Y, Katsuno M, Yamanaka K
Monomerization of TDP-43 is a key determinant for inducing TDP-43 pathology in amyotrophic lateral sclerosis.
Science Advances 9(31): eadf6895, 2023.

Press release from Nagoya Univ

2023/8/4 MEETING We gave presentations of our studies in The 46th Annual Meeting of the Japan Neuroscience Society (Sendai International Center).

Professor Dr. Yamanaka chaired the oral presentation session: "ALS".

Symposist Dr. Endo
Training Session For Early-Career Scientists (oral & poster)： Dr. Horiuchi
Poster Presentations: Dr. Komine, Dr. Watanabe, Dr. Kawade, Dr. Sobue, Dr. Shimohata, Mr. Sakai, Ms. Wang, Ms. Maekawa, Ms. Yanagisawa

2023/7/18 Dr. Fumito Endo has been back to our lab as Lecturer from UCLA.

2023/7/9 MEETING We gave presentations of our studies in The 66th Annual Meeting of the Japanese Society for Neurochemistry, The 64th Annual Meeting of the Japanese Society of Neuropathology: Joint Meeting （Kobe International Congress Center）.

Professor Dr. Yamanaka co-organized the asymposium entitled as "Neurology and Psychiatry research from the viewpoint of neuroinflammation, immunology, and pathology" with Associate Professor Dr. Izumi Kawachi (Niigata Univ).

Symposist： Dr. Watanabe
Poster Presentations: Mr. Sakai, Dr. Horiuchi

2023/6/29 Professor Dr. Yamanaka has been appointed President of the Japan Neuroscience Society.

Message from the President (Japan Neuroscience Society)

2023/6/17 RESEARCH Our review article on lipid metabolism in AD is now open in FEBS Open Bio:

Open Access
Kawade N & Yamanaka K
Novel insights into brain lipid metabolism in Alzheimer's disease: Oligodendrocytes and white matter abnormalities.
FEBS Open Bio 14(2): 194-196, 2023.

2023/5/22 RESEARCH Our work is now open in Journal of Bilogical Chemistry:

E40K mutation induces aggregation in canine SOD1, but not human SOD1; However, the mechanism remains unknown. We found that the species-specific aggregation depended on a difference of the 117th amino acid residues, methionine and leucine in canines and humans, respectively. Crystal structural analysis revealed the instability of the hydrophobic core in canine SOD1 because of 117th methionine creating a cavity, but the cavity was filled by 117th leucine. Instability of canine SOD1 due to the cavity is the basis of species-specific aggregation of SOD1, and a clue for developing novel therapeutics for canine DM.

Open Access
Hashimoto K, Watanabe S, Akutu M, Mukai N, Kamishina H, Furukawa Y, Yamanaka K
Intrinsic structural vulnerability in the hydrophobic core induces species-specific aggregation of canine SOD1 with degenerative myelopathy–linked E40K mutation.
Science Advances 9(31): eadf6895, 2023.

Press release from Nagoya Univ

2023/5/10 RESEARCH Our review article on neuroinflammation in AD is now open in Inflammation & Regeneration:

Open Access
Sobue A, Komine O, Yamanaka K
Neuroinflammation in Alzheimer’s disease: microglial signature and their relevance to disease.
Inflammation & Regeneration 43: 26, 2023.

2023/4/1 Dr. Shimohata joined to our lab. Drs. Komine and Watanabe became lecturers.

Our lab members in 2023.

2023/4/1 GRANT We are selected for Grant-in-Aid for Scientific Research in 2023 as follows:

Dr. Yamanaka: Grant-in-Aid for Scientific Research (A) (new)
Dr. Komine: Grant-in-Aid for Scientific Research (C) (continuing)
Dr. Watanabe: Grant-in-Aid for Scientific Research (C) (new)
Dr. Sobue: Grant-in-Aid for Early-Career Scientists (new)
Dr. Kawade: Grant-in-Aid for Early-Career Scientists (new)

Also, we are selected for
AMED-LEAP (collaboration)
AMED（Project for Elucidation of Mechanisms of Psychiatric and Neurological Diseases）
JST MOONSHOT R&D program (Performer)

Click here for our activities before 2023