Hederagenin and α-hederin promote degradation of proteins in neurodegenerative diseases and improve motor deficits in MPTP-mice

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• 作者：An-Guo Wu^a ; ¹ ; Wu Zeng^a ; ¹ ; Vincent Kam-Wai Wong^a ; Yi-Zhun Zhu^b ; Amy C.Y. Lo^c ; Liang Liu^a ; ^{lliu@must.edu.mo} ; Betty Yuen-Kwan Law^a ; ^{yklaw@must.edu.mo}
• 关键词：CHMs ; Chinese herbal medicines ; ATG ; autophagy-related proteins ; AD ; Alzheimer&rsquo ; s disease ; PD ; Parkinson&rsquo ; s disease ; AMPK ; 5&prime ; adenosine monophosphate-activated protein kinase ; mTOR ; mammalian target of rapamycin ; HD ; Huntington&rsquo ; s disease ; HH ; hedera helix ; PF ; petroleum ; MPTP ; 1-methyl-4-phenyl-1 ; 2 ; 3 ; 6-tetrahydropyridine ; EF ; ethylacetate fraction ; HTT ; huntingtin ; NF ; n-butanol ; GFP ; green fluorescent protein ; PE ; phosphatidylethanolamine ; AHS ; acid hydrolyzed solution ; CM
• 刊名：Pharmacological Research
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：115
• 期：Complete
• 页码：25-44
• 全文大小：7578 K
• 卷排序：115

文摘

Pathogenesis of neurodegenerative diseases such as Parkinson’s disease (PD) and Huntington’s disease (HD) are closely related to the formation of protein aggregates and inclusion body. For instance, active autophagic components from Chinese herbal medicines (CHMs) are highlighted to modulate neurodegeneration via degradation of disease proteins. In this study, the neuroprotective effect of the purified Hedera helix (HH) fraction containing both hederagenin and α-hederin, is confirmed by the improvement of motor deficits in PD mice model. Furthermore, hederagenin and α-hederin derived from HH are confirmed as novel autophagic enhancers. Both compounds reduce the protein level of mutant huntingtin with 74 CAG repeats and A53T α-synuclein, and inhibit the oligomerization of α-synuclein and inclusion formation of huntingtin, via AMPK-mTOR dependent autophagy induction. Both hederagenin and α-hederin induce autophagy and promote the degradation of neurodegenerative mutant disease proteins in vitro, suggesting the therapeutic roles of HH in neurodegenerative disorders.