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

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 disease...

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Autores principales:	Masatoshi Inden, Ayaka Takagi, Hazuki Kitai, Taisei Ito, Hisaka Kurita, Ryo Honda, Yuji O. Kamatari, Sora Nozaki, Xiaopeng Wen, Masanori Hijioka, Yoshihisa Kitamura, Isao Hozumi
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	α-synuclein synucleinopathies kaempferol Parkinson’s disease dementia with Lewy bodies multiple system atrophy Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/a7dc0a65bfb849738ef8075268babd97
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spelling	oai:doaj.org-article:a7dc0a65bfb849738ef8075268babd972021-11-11T16:56:49ZKaempferol Has Potent Protective and Antifibrillogenic Effects for α-Synuclein Neurotoxicity In Vitro10.3390/ijms2221114841422-00671661-6596https://doaj.org/article/a7dc0a65bfb849738ef8075268babd972021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11484https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Aggregation 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.Masatoshi IndenAyaka TakagiHazuki KitaiTaisei ItoHisaka KuritaRyo HondaYuji O. KamatariSora NozakiXiaopeng WenMasanori HijiokaYoshihisa KitamuraIsao HozumiMDPI AGarticleα-synucleinsynucleinopathieskaempferolParkinson’s diseasedementia with Lewy bodiesmultiple system atrophyBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11484, p 11484 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	α-synuclein synucleinopathies kaempferol Parkinson’s disease dementia with Lewy bodies multiple system atrophy Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	α-synuclein synucleinopathies kaempferol Parkinson’s disease dementia with Lewy bodies multiple system atrophy Biology (General) QH301-705.5 Chemistry QD1-999 Masatoshi Inden Ayaka Takagi Hazuki Kitai Taisei Ito Hisaka Kurita Ryo Honda Yuji O. Kamatari Sora Nozaki Xiaopeng Wen Masanori Hijioka Yoshihisa Kitamura Isao Hozumi Kaempferol Has Potent Protective and Antifibrillogenic Effects for α-Synuclein Neurotoxicity In Vitro
description	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.
format	article
author	Masatoshi Inden Ayaka Takagi Hazuki Kitai Taisei Ito Hisaka Kurita Ryo Honda Yuji O. Kamatari Sora Nozaki Xiaopeng Wen Masanori Hijioka Yoshihisa Kitamura Isao Hozumi
author_facet	Masatoshi Inden Ayaka Takagi Hazuki Kitai Taisei Ito Hisaka Kurita Ryo Honda Yuji O. Kamatari Sora Nozaki Xiaopeng Wen Masanori Hijioka Yoshihisa Kitamura Isao Hozumi
author_sort	Masatoshi Inden
title	Kaempferol Has Potent Protective and Antifibrillogenic Effects for α-Synuclein Neurotoxicity In Vitro
title_short	Kaempferol Has Potent Protective and Antifibrillogenic Effects for α-Synuclein Neurotoxicity In Vitro
title_full	Kaempferol Has Potent Protective and Antifibrillogenic Effects for α-Synuclein Neurotoxicity In Vitro
title_fullStr	Kaempferol Has Potent Protective and Antifibrillogenic Effects for α-Synuclein Neurotoxicity In Vitro
title_full_unstemmed	Kaempferol Has Potent Protective and Antifibrillogenic Effects for α-Synuclein Neurotoxicity In Vitro
title_sort	kaempferol has potent protective and antifibrillogenic effects for α-synuclein neurotoxicity in vitro
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/a7dc0a65bfb849738ef8075268babd97
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Kaempferol Has Potent Protective and Antifibrillogenic Effects for α-Synuclein Neurotoxicity In Vitro

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