PMID- 26792101 OWN - NLM STAT- MEDLINE DCOM- 20170106 LR - 20220317 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 6 DP - 2016 Jan 21 TI - Acupuncture promotes mTOR-independent autophagic clearance of aggregation-prone proteins in mouse brain. PG - 19714 LID - 10.1038/srep19714 [doi] LID - 19714 AB - Acupuncture has historically been practiced to treat medical disorders by mechanically stimulating specific acupoints with fine needles. Despite its well-documented efficacy, its biological basis remains largely elusive. In this study, we found that mechanical stimulation at the acupoint of Yanglingquan (GB34) promoted the autophagic clearance of alpha-synuclein (alpha-syn), a well known aggregation-prone protein closely related to Parkinson's disease (PD), in the substantia nigra par compacta (SNpc) of the brain in a PD mouse model. We found the protein clearance arose from the activation of the autophagy-lysosome pathway (ALP) in a mammalian target of rapamycin (mTOR)-independent approach. Further, we observed the recovery in the activity of dopaminergic neurons in SNpc, and improvement in the motor function at the behavior level of PD mice. Whereas acupuncture and rapamycin, a chemical mTOR inhibitor, show comparable alpha-syn clearance and therapeutic effects in the PD mouse model, the latter adopts a distinctly different, mTOR-dependent, autophagy induction process. Due to this fundamental difference, acupuncture may circumvent adverse effects of the rapamycin treatment. The newly discovered connection between acupuncture and autophagy not only provides a new route to understanding the molecular mechanism of acupuncture but also sheds new light on cost-effective and safe therapy of neurodegenerative diseases. FAU - Tian, Tian AU - Tian T AD - Division of Physical Biology &Bioimaging Center, Shanghai Synchrotron Radiation Facility, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China. FAU - Sun, Yanhong AU - Sun Y AD - Division of Physical Biology &Bioimaging Center, Shanghai Synchrotron Radiation Facility, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China. FAU - Wu, Huangan AU - Wu H AD - Shanghai Institute of Acupuncture Moxibustion and Meridian, Shanghai University of Traditional Chinese Medicine, Shanghai 200030, China. FAU - Pei, Jian AU - Pei J AD - Department of Acupuncture and Moxibustion, Long Hua Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China. FAU - Zhang, Jing AU - Zhang J AD - College of Acumox and Tuina, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. FAU - Zhang, Yi AU - Zhang Y AD - Division of Physical Biology &Bioimaging Center, Shanghai Synchrotron Radiation Facility, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China. FAU - Wang, Lu AU - Wang L AD - Division of Physical Biology &Bioimaging Center, Shanghai Synchrotron Radiation Facility, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China. FAU - Li, Bin AU - Li B AD - Division of Physical Biology &Bioimaging Center, Shanghai Synchrotron Radiation Facility, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China. FAU - Wang, Lihua AU - Wang L AD - Division of Physical Biology &Bioimaging Center, Shanghai Synchrotron Radiation Facility, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China. FAU - Shi, Jiye AU - Shi J AD - Kellogg College, University of Oxford, Banbury Road, Oxford, OX2 6PN, UK. AD - UCB Pharma, 208 Bath Road, Slough, SL1 3WE, UK. FAU - Hu, Jun AU - Hu J AD - Division of Physical Biology &Bioimaging Center, Shanghai Synchrotron Radiation Facility, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China. FAU - Fan, Chunhai AU - Fan C AD - Division of Physical Biology &Bioimaging Center, Shanghai Synchrotron Radiation Facility, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160121 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Protein Aggregates) RN - 0 (alpha-Synuclein) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - *Acupuncture MH - Acupuncture Therapy MH - Animals MH - *Autophagy MH - Brain/*metabolism/pathology MH - Disease Models, Animal MH - Dopaminergic Neurons/metabolism MH - Lysosomes/metabolism MH - Male MH - Mice MH - Neurons/metabolism/ultrastructure MH - Parkinson Disease/metabolism/pathology/therapy MH - Protein Aggregates MH - Protein Aggregation, Pathological/metabolism MH - Signal Transduction MH - Substantia Nigra/metabolism/pathology MH - TOR Serine-Threonine Kinases/*metabolism MH - alpha-Synuclein/*metabolism PMC - PMC4726430 COIS- The authors declare no competing financial interests. EDAT- 2016/01/23 06:00 MHDA- 2017/01/07 06:00 PMCR- 2016/01/21 CRDT- 2016/01/22 06:00 PHST- 2015/09/15 00:00 [received] PHST- 2015/12/07 00:00 [accepted] PHST- 2016/01/22 06:00 [entrez] PHST- 2016/01/23 06:00 [pubmed] PHST- 2017/01/07 06:00 [medline] PHST- 2016/01/21 00:00 [pmc-release] AID - srep19714 [pii] AID - 10.1038/srep19714 [doi] PST - epublish SO - Sci Rep. 2016 Jan 21;6:19714. doi: 10.1038/srep19714.