Neferine Attenuates the Protein Level and Toxicity of Mutant Huntingtin in PC-12 Cells via Induction of Autophagy

Bibliographic Details
Title: Neferine Attenuates the Protein Level and Toxicity of Mutant Huntingtin in PC-12 Cells via Induction of Autophagy
Authors: Vincent Kam Wai Wong, An Guo Wu, Jing Rong Wang, Liang Liu, Betty Yuen-Kwan Law
Source: Molecules, Vol 20, Iss 3, Pp 3496-3514 (2015)
Publisher Information: MDPI AG, 2015.
Publication Year: 2015
Collection: LCC:Organic chemistry
Subject Terms: autophagy, Nelumbo nucifera, neferine, AMPK, mTOR, a-synuclein, huntingtin, PC-12, bioactivity, natural products, mechanism of action, Organic chemistry, QD241-441
More Details: 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.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1420-3049
Relation: http://www.mdpi.com/1420-3049/20/3/3496; https://doaj.org/toc/1420-3049
DOI: 10.3390/molecules20033496
Access URL: https://doaj.org/article/a11046933fd04509a870988dc18cab1b
Accession Number: edsdoj.11046933fd04509a870988dc18cab1b
Database: Directory of Open Access Journals
More Details
ISSN:14203049
DOI:10.3390/molecules20033496
Published in:Molecules
Language:English