title: Acupuncture promotes mTOR-independent autophagic clearance of aggregation-prone proteins in mouse brain.
abstract: 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 α-synuclein (α-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 α-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.
authors.affiliation: 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.
authors.forename: Tian
authors.initials: T
authors.lastname: Tian
authors.affiliation: 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.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Shanghai Institute of Acupuncture Moxibustion and Meridian, Shanghai University of Traditional Chinese Medicine, Shanghai 200030, China.
authors.forename: Huangan
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Acupuncture and Moxibustion, Long Hua Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Pei
authors.affiliation: College of Acumox and Tuina, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Lihua
authors.initials: L
authors.lastname: Wang
authors.affiliation: Kellogg College, University of Oxford, Banbury Road, Oxford, OX2 6PN, UK.|UCB Pharma, 208 Bath Road, Slough, SL1 3WE, UK.
authors.forename: Jiye
authors.initials: J
authors.lastname: Shi
authors.affiliation: 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.
authors.forename: Jun
authors.initials: J
authors.lastname: Hu
authors.affiliation: 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.
authors.forename: Chunhai
authors.initials: C
authors.lastname: Fan
mesh_terms: D026881:Acupuncture; D015670:Acupuncture Therapy; D000818:Animals; D001343:Autophagy; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D051379:Mice; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D066329:Protein Aggregates; D066263:Protein Aggregation, Pathological / Q000378:metabolism; D015398:Signal Transduction; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D066329:Protein Aggregates; D051844:alpha-Synuclein; D058570:TOR Serine-Threonine Kinases