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Title: Perampanel Inhibits α‐Synuclein Transmission in Parkinson's Disease Models
Authors: Ueda, Jun
Uemura, Norihito
Sawamura, Masanori
Taguchi, Tomoyuki
Ikuno, Masashi
Kaji, Seiji
Taruno, Yosuke
Matsuzawa, Shuichi
Yamakado, Hodaka
Takahashi, Ryosuke
Author's alias: 上田, 潤
上村, 紀仁
澤村, 正典
田口, 智之
生野, 真嗣
梶, 誠兒
樽野, 陽亮
松澤, 秀一
山門, 穂高
髙橋, 良輔
Keywords: Parkinson's disease
α‐synuclein
neuronal activity
perampanel
macropinocytosis
Issue Date: Apr-2021
Publisher: Wiley
Journal title: Movement disorders : official journal of the Movement Disorder Society
Thesis number: 28558
Abstract: [Background]: The intercellular transmission of pathogenic proteins plays a key role in the clinicopathological progression of neurodegenerative diseases. Previous studies have demonstrated that this uptake and release process is regulated by neuronal activity. [Objective]: The objective of this study was to examine the effect of perampanel, an antiepileptic drug, on α‐synuclein transmission in cultured cells and mouse models of Parkinson's disease.Methods: Mouse primary hippocampal neurons were transduced with α‐synuclein preformed fibrils to examine the effect of perampanel on the development of α‐synuclein pathology and its mechanisms of action. An α‐synuclein preformed fibril‐injected mouse model was used to validate the effect of oral administration of perampanel on the α‐synuclein pathology in vivo. [Results]: Perampanel inhibited the development of α‐synuclein pathology in mouse hippocampal neurons transduced with α‐synuclein preformed fibrils. Interestingly, perampanel blocked the neuronal uptake of α‐synuclein preformed fibrils by inhibiting macropinocytosis in a neuronal activity‐dependent manner. We confirmed that oral administration of perampanel ameliorated the development of α‐synuclein pathology in wild‐type mice inoculated with α‐synuclein preformed fibrils.[Conclusion]: Modulation of neuronal activity could be a promising therapeutic target for Parkinson's disease, and perampanel could be a novel disease‐modifying drug for Parkinson's disease.
Description: パーキンソン病モデルへのペランパネルの有効性を確認 --パーキンソン病の進行抑制治療への期待--. 京都大学プレスリリース. 2021-04-05.
Rights: 発行元の許可を得て登録しています。
This is the peer reviewed version of the following article: Jun Ueda, et. al. Perampanel Inhibits α‐Synuclein Transmission in Parkinson's Disease Models. Movement disorders : official journal of the Movement Disorder Society. 2021, 28558., which has been published in final form at https://doi.org/10.1002/mds.28558. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
The full-text file will be made open to the public on 04 April 2022 in accordance with publisher's 'Terms and Conditions for Self-Archiving'
This is not the published version. Please cite only the published version.
この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。
URI: http://hdl.handle.net/2433/262704
DOI(Published Version): 10.1002/mds.28558
PubMed ID: 33813737
Related Link: https://www.kyoto-u.ac.jp/ja/research-news/2021-04-05
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