Balancing mTOR Signaling and Autophagy in the Treatment of Parkinson's Disease

Int J Mol Sci. 2019 Feb 8;20(3):728. doi: 10.3390/ijms20030728.

Abstract

The mammalian target of rapamycin (mTOR) signaling pathway plays a critical role in regulating cell growth, proliferation, and life span. mTOR signaling is a central regulator of autophagy by modulating multiple aspects of the autophagy process, such as initiation, process, and termination through controlling the activity of the unc51-like kinase 1 (ULK1) complex and vacuolar protein sorting 34 (VPS34) complex, and the intracellular distribution of TFEB/TFE3 and proto-lysosome tubule reformation. Parkinson's disease (PD) is a serious, common neurodegenerative disease characterized by dopaminergic neuron loss in the substantia nigra pars compacta (SNpc) and the accumulation of Lewy bodies. An increasing amount of evidence indicates that mTOR and autophagy are critical for the pathogenesis of PD. In this review, we will summarize recent advances regarding the roles of mTOR and autophagy in PD pathogenesis and treatment. Further characterizing the dysregulation of mTOR pathway and the clinical translation of mTOR modulators in PD may offer exciting new avenues for future drug development.

Keywords: Parkinson’s disease; autophagy; mTOR.

Publication types

  • Review

MeSH terms

  • Animals
  • Autophagy / drug effects
  • Autophagy / genetics
  • Biomarkers
  • Carrier Proteins / metabolism
  • Humans
  • Molecular Targeted Therapy
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / etiology
  • Parkinson Disease / metabolism*
  • Protein Binding
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Signal Transduction / drug effects*
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Biomarkers
  • Carrier Proteins
  • Protein Kinase Inhibitors
  • TOR Serine-Threonine Kinases