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Curcumin Ameliorates the Neurodegenerative Pathology in A53T α-synuclein Cell Model of Parkinson's Disease Through the Downregulation of mTOR/p70S6K Signaling and the Recovery of Macroautophagy.
MedLine Citation:
PMID:  23325107     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Parkinson's disease (PD) is pathologically characterized by the presence of α-synuclein positive intracytoplasmic inclusions. The missense mutation, A53T α-synuclein is closely related to hereditary, early-onset PD. Accumulating evidences suggest that pathological accumulation of A53T α-synuclein protein will perturb itself to be efficiently and normally degraded through its usual degradation pathway, macroautophagy-lysosome pathway, therefore toxic effects on the neuron will be exacerbated. Based on the above fact, we demonstrated in this study that A53T α-synuclein overexpression impairs macroautophagy in SH-SY5Y cells and upregulates mammalian target of rapamycin (mTOR)/p70 ribosomal protein S6 kinase (p70S6K) signaling, the classical suppressive pathway of autophagy. We further found that curcumin, a natural compound derived from the curry spice turmeric and with low toxicity in normal cells, could efficiently reduce the accumulation of A53T α-synuclein through downregulation of the mTOR/p70S6K signaling and recovery of macroautophagy which was suppressed. These findings suggested that the regulation of mTOR/p70S6K signaling may be a participant of the accumulation of A53T α-synuclein protein-linked Parkinsonism. Meanwhile curcumin could be a candidate neuroprotective agent by inducing macroautophagy, and needs to be further investigated by clinical application in patients suffering Parkinson's disease.
Authors:
Tian-Fang Jiang; Ying-Jie Zhang; Hai-Yan Zhou; Hong-Mei Wang; Li-Peng Tian; Jun Liu; Jian-Qing Ding; Sheng-Di Chen
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-17
Journal Detail:
Title:  Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology     Volume:  -     ISSN:  1557-1904     ISO Abbreviation:  J Neuroimmune Pharmacol     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101256586     Medline TA:  J Neuroimmune Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Neurology & Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.
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