title: Hederagenin and α-hederin promote degradation of proteins in neurodegenerative diseases and improve motor deficits in MPTP-mice.
abstract: 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.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China.
authors.forename: An-Guo
authors.initials: AG
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China.
authors.forename: Wu
authors.initials: W
authors.lastname: Zeng
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China.
authors.forename: Vincent Kam-Wai
authors.initials: VK
authors.lastname: Wong
authors.affiliation: School of Pharmacy, Macau University of Science and Technology, Macau, China.
authors.forename: Yi-Zhun
authors.initials: YZ
authors.lastname: Zhu
authors.affiliation: Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
authors.forename: Amy C Y
authors.initials: AC
authors.lastname: Lo
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China. Electronic address: lliu@must.edu.mo.
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China. Electronic address: yklaw@must.edu.mo.
authors.forename: Betty Yuen-Kwan
authors.initials: BY
authors.lastname: Law
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000378:metabolism*; D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D005260:Female; D035981:Hedera / Q000737:chemistry; D000071058:Huntingtin Protein / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D016716:PC12 Cells; D051381:Rats; D012503:Saponins / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; D000071058:Huntingtin Protein; D012503:Saponins; D051844:alpha-Synuclein; C010177:beta-hederin; D009828:Oleanolic Acid; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D058570:TOR Serine-Threonine Kinases; D000263:Adenylate Kinase; C025763:hederagenin
keywords: Autophagy; Hedera helix; Hederagenin; Huntingtin; α-Hederin; α-Synuclein