title: 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: Department of Neurology & Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
authors: Tian-Fang
authors: TF
authors: Jiang
authors: Ying-Jie
authors: YJ
authors: Zhang
authors: Hai-Yan
authors: HY
authors: Zhou
authors: Hong-Mei
authors: HM
authors: Wang
authors: Li-Peng
authors: LP
authors: Tian
authors: Jun
authors: J
authors: Liu
authors: Jian-Qing
authors: JQ
authors: Ding
authors: Sheng-Di
authors: SD
authors: Chen
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects*; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D005822:Genetic Vectors; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000187:drug effects*; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000473:pathology*; D018696:Neuroprotective Agents; D010300:Parkinson Disease / Q000188:drug therapy* / Q000473:pathology*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000502:physiology*; D014162:Transfection; D051844:alpha-Synuclein / Q000502:physiology*
chemical_list: D018696:Neuroprotective Agents; D051844:alpha-Synuclein; C025946:3-methyladenine; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D003474:Curcumin; D000225:Adenine