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

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 c...

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Published in:International journal of molecular sciences 2019-02, Vol.20 (3), p.728
Main Authors: Zhu, Zhou, Yang, Chuanbin, Iyaswamy, Ashok, Krishnamoorthi, Senthilkumar, Sreenivasmurthy, Sravan Gopalkrishnashetty, Liu, Jia, Wang, Ziying, Tong, Benjamin Chun-Kit, Song, Juxian, Lu, Jiahong, Cheung, King-Ho, Li, Min
Format: Article
Language:English
Subjects:
AKT protein
Autophagy
Binding sites
Biosynthesis
Blood-brain barrier
Cell cycle
Cell growth
Cleavage
Disease
Elongation
Feedback loops
Growth factors
Kinases
Lysosomes
Metabolism
MPTP
Mutation
Nuclear transport
Parkinson's disease
Phagocytosis
Phosphorylation
Positive feedback
Protein synthesis
Proteins
Review
TOR protein
Transcription factors
Tubules
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Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms20030728