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.

Abstract

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
• Journal: Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology (J Neuroimmune Pharmacol) Vol. 8 Issue 1 Pg. 356-69 (Mar 2013) ISSN: 1557-1904 [Electronic] United States
• PMID: 23325107 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Neuroprotective Agents
• alpha-Synuclein
• 3-methyladenine
• Ribosomal Protein S6 Kinases, 70-kDa
• TOR Serine-Threonine Kinases
• Curcumin
• Adenine

Topics

• Adenine (analogs & derivatives, pharmacology)
• Autophagy (drug effects)
• Blotting, Western
• Cell Line
• Cell Survival (drug effects)
• Curcumin (pharmacology)
• Genetic Vectors
• Humans
• Immunohistochemistry
• Macrophages (drug effects)
• Neurodegenerative Diseases (drug therapy, pathology)
• Neuroprotective Agents
• Parkinson Disease (drug therapy, pathology)
• Ribosomal Protein S6 Kinases, 70-kDa (physiology)
• TOR Serine-Threonine Kinases (physiology)
• Transfection
• alpha-Synuclein (physiology)