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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 |
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creator | 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 |
description | 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. |
doi_str_mv | 10.3390/ijms20030728 |
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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.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms20030728</identifier><identifier>PMID: 30744070</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>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</subject><ispartof>International journal of molecular sciences, 2019-02, Vol.20 (3), p.728</ispartof><rights>2019. This work is licensed under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 by the authors. 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c478t-a0d9f9f952b516718cf77a9f16eab42f8ba6c5b0f61727547a920f17aae358073</citedby><cites>FETCH-LOGICAL-c478t-a0d9f9f952b516718cf77a9f16eab42f8ba6c5b0f61727547a920f17aae358073</cites><orcidid>0000-0002-0112-9274 ; 0000-0002-0642-8919 ; 0000-0001-8288-4038</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2332022711/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2332022711?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,25730,27900,27901,36988,36989,44565,53765,53767,75095</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30744070$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhu, Zhou</creatorcontrib><creatorcontrib>Yang, Chuanbin</creatorcontrib><creatorcontrib>Iyaswamy, Ashok</creatorcontrib><creatorcontrib>Krishnamoorthi, Senthilkumar</creatorcontrib><creatorcontrib>Sreenivasmurthy, Sravan Gopalkrishnashetty</creatorcontrib><creatorcontrib>Liu, Jia</creatorcontrib><creatorcontrib>Wang, Ziying</creatorcontrib><creatorcontrib>Tong, Benjamin Chun-Kit</creatorcontrib><creatorcontrib>Song, Juxian</creatorcontrib><creatorcontrib>Lu, Jiahong</creatorcontrib><creatorcontrib>Cheung, King-Ho</creatorcontrib><creatorcontrib>Li, Min</creatorcontrib><title>Balancing mTOR Signaling and Autophagy in the Treatment of Parkinson's Disease</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>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.</description><subject>AKT protein</subject><subject>Autophagy</subject><subject>Binding sites</subject><subject>Biosynthesis</subject><subject>Blood-brain barrier</subject><subject>Cell cycle</subject><subject>Cell growth</subject><subject>Cleavage</subject><subject>Disease</subject><subject>Elongation</subject><subject>Feedback loops</subject><subject>Growth factors</subject><subject>Kinases</subject><subject>Lysosomes</subject><subject>Metabolism</subject><subject>MPTP</subject><subject>Mutation</subject><subject>Nuclear transport</subject><subject>Parkinson's disease</subject><subject>Phagocytosis</subject><subject>Phosphorylation</subject><subject>Positive feedback</subject><subject>Protein synthesis</subject><subject>Proteins</subject><subject>Review</subject><subject>TOR protein</subject><subject>Transcription 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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.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>30744070</pmid><doi>10.3390/ijms20030728</doi><orcidid>https://orcid.org/0000-0002-0112-9274</orcidid><orcidid>https://orcid.org/0000-0002-0642-8919</orcidid><orcidid>https://orcid.org/0000-0001-8288-4038</orcidid><oa>free_for_read</oa></addata></record> |
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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 |
title | Balancing mTOR Signaling and Autophagy in the Treatment of Parkinson's Disease |
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