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

J Neuroimmune Pharmacol. 2013 Mar;8(1):356-69. doi: 10.1007/s11481-012-9431-7. Epub 2013 Jan 17.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / 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*
  • Neurodegenerative Diseases / pathology*
  • Neuroprotective Agents*
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / pathology*
  • Ribosomal Protein S6 Kinases, 70-kDa / physiology*
  • TOR Serine-Threonine Kinases / physiology*
  • Transfection
  • alpha-Synuclein / physiology*

Substances

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