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Molecules 2015, 20(3), 3496-3514; doi:10.3390/molecules20033496

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

State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China
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Academic Editor: Isabel C. F. R. Ferreira
Received: 18 December 2014 / Revised: 11 February 2015 / Accepted: 13 February 2015 / Published: 18 February 2015
(This article belongs to the Collection Bioactive Compounds)
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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. View Full-Text
Keywords: autophagy; Nelumbo nucifera; neferine; AMPK; mTOR; a-synuclein; huntingtin; PC-12; bioactivity; natural products; mechanism of action autophagy; Nelumbo nucifera; neferine; AMPK; mTOR; a-synuclein; huntingtin; PC-12; bioactivity; natural products; mechanism of action
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Wong, V.K.W.; Wu, A.G.; Wang, J.R.; Liu, L.; Law, B.Y.-K. Neferine Attenuates the Protein Level and Toxicity of Mutant Huntingtin in PC-12 Cells via Induction of Autophagy. Molecules 2015, 20, 3496-3514.

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