Balancing mTOR signaling and autophagy in the treatment of Parkinson’s disease

Zhou Zhu, Chuanbin YANG, Ashok IYASWAMY, Senthilkumar Krishnamoorthi, Sravan Gopalkrishnashetty Sreenivasmurthy, Jia Liu, Ziying Wang, Chun Kit Benjamin TONG, Juxian SONG, Jiahong Lu, King-Ho CHEUNG, Min LI*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

41 Citations (Scopus)

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.

Original languageEnglish
Article number728
JournalInternational Journal of Molecular Sciences
Volume20
Issue number3
DOIs
Publication statusPublished - 1 Feb 2019

Scopus Subject Areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

User-Defined Keywords

  • Autophagy
  • mTOR
  • Parkinson’s disease

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