| 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. | |
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MedLine Citation:
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PMID: 23325107 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: JOURNAL ARTICLE Date: 2013-1-17 |
Journal Detail:
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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:
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Created Date: 2013-1-17 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101256586 Medline TA: J Neuroimmune Pharmacol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Neurology & Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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