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論文 【 表示 ／ 非表示 】
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Sugiyama T, Murao N, Kadowaki H, Takao K, Miyakawa T, Matsushita Y, Katagiri T, Futatsugi A, Shinmyo Y, Kawasaki H, Sakai J, Shiomi K, Nakazato M, Takeda K, Mikoshiba K, Ploegh HL, Ichijo H, Nishitoh H.
iScience 24 ( 7 ) 102758 2021年1月
担当区分：筆頭著者 記述言語：英語 掲載種別：学位論文（博士） 出版者・発行元：iScience
Derlin family members (Derlins) are primarily known as components of the endoplasmic reticulum-associated degradation pathway that eliminates misfolded proteins. Here we report a function of Derlins in the brain development. Deletion of Derlin-1 or Derlin-2 in the central nervous system of mice impaired postnatal brain development, particularly of the cerebellum and striatum, and induced motor control deficits. Derlin-1 or Derlin-2 deficiency reduced neurite outgrowth in vitro and in vivo and surprisingly also inhibited sterol regulatory element binding protein 2 (SREBP-2)-mediated brain cholesterol biosynthesis. In addition, reduced neurite outgrowth due to Derlin-1 deficiency was rescued by SREBP-2 pathway activation. Overall, our findings demonstrate that Derlins sustain brain cholesterol biosynthesis, which is essential for appropriate postnatal brain development and function.
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Sugiyama T, Murao N, Kadowaki H, Nishitoh H
Scientific reports 12 ( 1 ) 21840 - 21840 2022年12月
担当区分：筆頭著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Scientific Reports
There are no available therapies targeting the underlying molecular mechanisms of neurodegenerative diseases. Although chaperone therapies that alleviate endoplasmic reticulum (ER) stress recently showed promise in the treatment of neurodegenerative diseases, the detailed mechanisms remain unclear. We previously reported that mice with central nervous system-specific deletion of Derlin-1, which encodes an essential component for ER quality control, are useful as models of neurodegenerative diseases such as spinocerebellar degeneration. Cholesterol biosynthesis is essential for brain development, and its disruption inhibits neurite outgrowth, causing brain atrophy. In this study, we report a novel mechanism by which chemical chaperones ameliorate brain atrophy and motor dysfunction. ER stress was induced in the cerebella of Derlin-1 deficiency mice, whereas the administration of a chemical chaperone did not alleviate ER stress. However, chemical chaperone treatment ameliorated cholesterol biosynthesis impairment through SREBP-2 activation and simultaneously relieved brain atrophy and motor dysfunction. Altogether, these findings demonstrate that ER stress may not be the target of action of chaperone therapies and that chemical chaperone-mediated improvement of brain cholesterol biosynthesis is a promising novel therapeutic strategy for neurodegenerative diseases.
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Sugiyama T., Nishitoh H.
Journal of Biochemistry 176 ( 3 ) 179 - 186 2024年9月
担当区分：筆頭著者, 責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Biochemistry
Aberrant proteostasis is thought to be involved in the pathogenesis of neurodegenerative diseases. Some proteostasis abnormalities are ameliorated by chaperones. Chaperones are divided into three groups: molecular, pharmacological and chemical. Chemical chaperones intended to alleviate stress in organelles, such as the endoplasmic reticulum (ER), are now being administered clinically. Of the chemical chaperones, 4-phenylbutyrate (4-PBA) has been used as a research reagent, and its mechanism of action includes chaperone effects and the inhibition of histone deacetylase. Moreover, it also binds to the B-site of SEC24 and regulates COPII-mediated transport from the ER. Although its therapeutic effect may not be strong, elucidating the mechanism of action of 4-PBA may contribute to the identification of novel therapeutic targets for neurodegenerative diseases.
DOI： 10.1093/jb/mvae048
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Sugiyama T., Ishii N., Ebihara Y., Shiomi K., Mochizuki H.
International Journal of Environmental Research and Public Health 18 ( 20 ) 10749 - 10749 2021年10月
担当区分：筆頭著者, 責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：International Journal of Environmental Research and Public Health
As a result of population growth and the development of tube wells, humans’ exposure to arsenic has increased over the past few decades. The natural course of organ damage secondary to arsenic exposure is not yet well understood. In Toroku, Japan, an arsenic mine was intermittently operated from 1920 to 1962, and residents were exposed to high concentrations of arsenic. In this paper, we analyzed 190 consecutive residents for whom detailed records of neurological symptoms and findings were obtained from 1974 to 2005. All participants were interviewed regarding the presence of general, skin, hearing, respiratory, and neurological symptoms. Neurological symptoms were classified into extremity numbness or pain, constipation, dyshidrosis, sensory loss, and muscle atrophy. Superficial and vibratory sensation was also evaluated. More than 80% of participants experienced extremity numbness, and numbness was the most common neurological symptom. Numbness was associated with superficial sensory disturbance, and was correlated with the subsequent development of other neurological symptoms, including autonomic and motor symptoms. No previous studies have investigated the natural course of chronic arsenic intoxication; thus, these data serve as a guide for detecting early symptoms due to arsenic exposure.
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Disinhibited blink reflex recovery is related to lateral trunk flexion in Parkinson disease 査読あり
Sugiyama T., Mochizuki H., Hara Y., Miyamoto M., Nakazato Y., Taniguchi A., Ishii N., Shiomi K., Nakazato M.
Journal of Clinical Neurophysiology 35 ( 4 ) 346 - 350 2018年
担当区分：筆頭著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Clinical Neurophysiology
Copyright © 2018 by the American Clinical Neurophysiology Society Purpose: Lateral trunk flexion is often observed in patients with Parkinson disease (PD) and causes poor quality of life. Asymmetrical function of the basal ganglia is believed to be the main cause of lateral trunk flexion, and dysfunction of the basal ganglia facilitates the blink reflex by disinhibiting the spinal trigeminal nucleus. Our aim was to investigate whether a disinhibited blink reflex recovery curve (BRrc) was associated with lateral trunk flexion in PD patients. Methods: We enrolled 21 PD patients, including 11 with marked lateral trunk flexion (F-PD) and 10 with normal posture (N-PD), and 10 normal controls. Blink reflex recovery curves at interstimulus intervals of 200, 300, and 500 ms were compared between F-PD N-PD and normal controls. Results: The BRrc in F-PD patients was more disinhibited than in N-PD patients and controls, and this disinhibition was asymmetrical. Conclusions: The asymmetrically disinhibited BRrc in F-PD patients was associated with lateral trunk flexion. This is the first neurophysiological study of patients with PD with abnormal posture. Examination of the BRrc may permit early detection of asymmetrical basal ganglia dysfunction that can eventually cause lateral trunk flexion.
MISC 【 表示 ／ 非表示 】
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コロナワクチン後に生じたと考えられる脳脊髄液減少症により体位性頻脈発作を認めた一例
長友優菜, 金丸和樹, 杉山崇史, 宮本美由貴, 酒井克也, 中里祐毅, 望月仁志, 塩見一剛
臨床神経学(Web) 61 ( 12 ) 2021年
講演・口頭発表等 【 表示 ／ 非表示 】
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抗横紋筋抗体陽性の筋炎・心筋炎合併重症筋無力症（MG）に対するエフガルチギモド治療経験
田中啓文、大窪隆一、末原雅人、神田佳樹、平方翔太、杉山崇史、塩見一剛
第243回日本神経学会九州地方会 2024年3月2日
開催年月日： 2024年3月2日
記述言語：日本語 会議種別：口頭発表（一般）
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神経症状発症前に神経伝導検査で異常を検出し得た CANVAS の1 例
宮本美由貴、酒井克也、中里祐毅、杉山崇史、輿水江里子、宮武聡子、松本直通、塩見一剛
第243回日本神経学会九州地方会 2024年3月2日
開催年月日： 2024年3月2日
記述言語：日本語 会議種別：口頭発表（一般）
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水頭症を合併したが積極的な髄液排出により日常生活に復帰することができたリステリア髄膜炎の2例
武田紘昌、酒井克也、金丸和樹、杉山崇史、中里祐毅、塩見一剛
第27回日本神経感染症学会総会 2023年10月13日
開催年月日： 2023年10月13日 - 2023年10月14日
記述言語：日本語 会議種別：口頭発表（一般）
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早期に眼瞼下垂を呈した悪性高熱症合併セントラルコア病の一例
宮本美由貴、武田紘昌、川上隆太郎、金丸和樹、酒井克也、中里祐毅、杉山崇史、西野一三、塩見一剛
第241回日本神経学会九州地方会 2023年9月23日
開催年月日： 2023年9月23日
記述言語：日本語 会議種別：口頭発表（一般）
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コレステロール合成に着目した神経変性に対するケミカルシャペロンの作用メカニズム
杉山崇史、村尾直哉、西頭英起
第66回日本神経化学会大会 2023年7月8日
開催年月日： 2023年7月6日 - 2023年7月8日
記述言語：日本語 会議種別：ポスター発表
受賞 【 表示 ／ 非表示 】
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ポスター賞
2018年11月 第13回小胞体ストレス研究会
杉山崇史
受賞区分：国内学会・会議・シンポジウム等の賞
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若手研究奨励賞
2018年10月 第13回日本臨床ストレス応答学会大会
杉山崇史
受賞区分：国内学会・会議・シンポジウム等の賞
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ポスター賞
2017年10月 第12回小胞体ストレス研究会
杉山崇史
受賞区分：国内学会・会議・シンポジウム等の賞
科研費（文科省・学振・厚労省）獲得実績 【 表示 ／ 非表示 】
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ALS新規治療標的開発に向けたコレステロール合成経路の役割の解明
研究課題/領域番号：24K18623 2024年04月 - 2027年03月
独立行政法人日本学術振興会 科学研究費基金 病態神経科学関連
担当区分：研究代表者