title: Neferine attenuates the protein level and toxicity of mutant huntingtin in PC-12 cells via induction of autophagy.
abstract: Mutant huntingtin aggregation is highly associated with the pathogenesis of Huntington's disease, an adult-onset autosomal dominant disorder, which leads to a loss of motor control and decline in cognitive function. Recent literature has revealed the protective role of autophagy in neurodegenerative diseases through degradation of mutant toxic proteins, including huntingtin or a-synuclein. Through the GFP-LC3 autophagy detection platform, we have  identified  neferine,  isolated  from  the  lotus  seed  embryo  of Nelumbo nucifera, which is able to induce autophagy through an AMPK-mTOR-dependent pathway. Furthermore, by overexpressing huntingtin with 74 CAG repeats (EGFP-HTT 74) in PC-12 cells, neferine reduces both the protein level and toxicity of mutant huntingtin through an autophagy-related gene 7 (Atg7)-dependent mechanism. With the variety of novel active compounds present in medicinal herbs, our current study suggests the possible protective mechanism of an autophagy inducer isolated from Chinese herbal medicine, which is crucial for its further development into a potential therapeutic agent for neurodegenerative disorders in the future.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China. kawwong@must.edu.mo.
authors.forename: Vincent Kam Wai
authors.initials: VK
authors.lastname: Wong
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China. wag1114@foxmail.com.
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. jrwang@must.edu.mo.
authors.forename: Jing Rong
authors.initials: JR
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China. 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. yklaw@must.edu.mo.
authors.forename: Betty Yuen-Kwan
authors.initials: BY
authors.lastname: Law
mesh_terms: D000328:Adult; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D044182:Benzylisoquinolines / Q000494:pharmacology*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016716:PC12 Cells; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D044182:Benzylisoquinolines; D004365:Drugs, Chinese Herbal; C086055:HTT protein, human; D000071058:Huntingtin Protein; D050505:Mutant Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C057222:neferine; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases