Kaempferol Has Potent Protective and Antifibrillogenic Effects for α-Synuclein Neurotoxicity In Vitro
| Autor: | Yuji O. Kamatari, Sora Nozaki, Isao Hozumi, Ryo Honda, Taisei Ito, Hisaka Kurita, Yoshihisa Kitamura, Hazuki Kitai, Xiaopeng Wen, Masanori Hijioka, Masatoshi Inden, Ayaka Takagi |
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| Rok vydání: | 2021 |
| Předmět: |
Programmed cell death
Amyloid Parkinson's disease QH301-705.5 animal diseases multiple system atrophy Pharmacology Protective Agents Neuroprotection Catalysis Article Inorganic Chemistry chemistry.chemical_compound Mice Neuroblastoma α-synuclein medicine Autophagy Animals heterocyclic compounds Physical and Theoretical Chemistry Biology (General) Kaempferols Molecular Biology QD1-999 Spectroscopy Synucleinopathies kaempferol Chemistry Basic Helix-Loop-Helix Leucine Zipper Transcription Factors Organic Chemistry Neurotoxicity synucleinopathies General Medicine medicine.disease Computer Science Applications nervous system diseases nervous system health occupations Parkinson’s disease alpha-Synuclein TFEB Neurotoxicity Syndromes Kaempferol dementia with Lewy bodies Lysosomes |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 11484, p 11484 (2021) International Journal of Molecular Sciences Volume 22 Issue 21 |
| ISSN: | 1422-0067 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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