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Perampanel Inhibits α‐Synuclein Transmission in Parkinson's Disease Models by Jun Ueda; Norihito Uemura; Masanori Sawamura; Tomoyuki Taguchi; Masashi Ikuno; Seiji Kaji; Yosuke Taruno; Shuichi Matsuzawa; Hodaka Yamakado; Ryosuke Takahashi is a Medicine article available to read on EtoBox.

What is Perampanel Inhibits α‐Synuclein Transmission in Parkinson's Disease Models about?

## 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 ameliora

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Author

Jun Ueda; Norihito Uemura; Masanori Sawamura; Tomoyuki Taguchi; Masashi Ikuno; Seiji Kaji; Yosuke Taruno; Shuichi Matsuzawa; Hodaka Yamakado; Ryosuke Takahashi

Publisher

Wiley

Published

2021

Language

EN

Field

Medicine (Health Sciences)