International Journal of Molecular Sciences | |
Kaempferol Has Potent Protective and Antifibrillogenic Effects for α-Synuclein Neurotoxicity In Vitro | |
Hazuki Kitai1  Taisei Ito1  Hisaka Kurita1  Masatoshi Inden1  Isao Hozumi1  Ayaka Takagi1  Sora Nozaki2  Masanori Hijioka2  Xiaopeng Wen2  Yoshihisa Kitamura2  Yuji O. Kamatari3  Ryo Honda3  | |
[1] Laboratory of Medical Therapeutics and Molecular Therapeutics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan;Laboratory of Pharmacology and Neurobiology, College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Noji-Higashi, Kusatsu 525-8577, Japan;The United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan; | |
关键词: α-synuclein; synucleinopathies; kaempferol; Parkinson’s disease; dementia with Lewy bodies; multiple system atrophy; | |
DOI : 10.3390/ijms222111484 | |
来源: DOAJ |
【 摘 要 】
Aggregation of α-synuclein (α-Syn) is implicated in the pathogenesis of Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Therefore, the removal of α-Syn aggregation could lead to the development of many new therapeutic agents for neurodegenerative diseases. In the present study, we succeeded in generating a new α-Syn stably expressing cell line using a piggyBac transposon system to investigate the neuroprotective effect of the flavonoid kaempferol on α-Syn toxicity. We found that kaempferol provided significant protection against α-Syn-related neurotoxicity. Furthermore, kaempferol induced autophagy through an increase in the biogenesis of lysosomes by inducing the expression of transcription factor EB and reducing the accumulation of α-Syn; thus, kaempferol prevented neuronal cell death. Moreover, kaempferol directly blocked the amyloid fibril formation of α-Syn. These results support the therapeutic potential of kaempferol in diseases such as synucleinopathies that are characterized by α-Syn aggregates.
【 授权许可】
Unknown