Kaempferol Has Potent Protective and Antifibrillogenic Effects for α-Synuclein Neurotoxicity In Vitro

International Journal of Molecular Sciences

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