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

Aggregation of alpha-synuclein (alpha-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 alpha-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 alpha-Syn stably expressing cell line using a piggyBac transposon system to investigate the neuroprotective effect of the flavonoid kaempferol on alpha-Syn toxicity. We found that kaempferol provided significant protection against alpha-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 alpha-Syn; thus, kaempferol prevented neuronal cell death. Moreover, kaempferol directly blocked the amyloid fibril formation of alpha-Syn. These results support the therapeutic potential of kaempferol in diseases such as synucleinopathies that are characterized by alpha-Syn aggregates.