PMID- 33161784
OWN - NLM
STAT- MEDLINE
DCOM- 20211203
LR  - 20220920
IS  - 1744-8360 (Electronic)
IS  - 1473-7175 (Print)
IS  - 1473-7175 (Linking)
VI  - 21
IP  - 1
DP  - 2021 Jan
TI  - Metformin as a potential therapeutic for neurological disease: mobilizing AMPK to 
      repair the nervous system.
PG  - 45-63
LID - 10.1080/14737175.2021.1847645 [doi]
AB  - Introduction: Metformin is currently first line therapy for type 2 diabetes 
      (T2D). The mechanism of action of metformin involves activation of AMP-activated 
      protein kinase (AMPK) to enhance mitochondrial function (for example, biogenesis, 
      refurbishment and dynamics) and autophagy. Many neurodegenerative diseases of the 
      central and peripheral nervous systems arise from metabolic failure and toxic 
      protein aggregation where activated AMPK could prove protective. Areas covered: 
      The authors review literature on metformin treatment in Parkinson's disease, 
      Huntington's disease and other neurological diseases of the CNS along with 
      neuroprotective effects of AMPK activation and suppression of the mammalian 
      target of rapamycin (mTOR) pathway on peripheral neuropathy and neuropathic pain. 
      The authors compare the efficacy of metformin with the actions of resveratrol. 
      Expert opinion: Metformin, through activation of AMPK and autophagy, can enhance 
      neuronal bioenergetics, promote nerve repair and reduce toxic protein aggregates 
      in neurological diseases. A long history of safe use in humans should encourage 
      development of metformin and other AMPK activators in preclinical and clinical 
      research. Future studies in animal models of neurological disease should strive 
      to further dissect in a mechanistic manner the pathways downstream from 
      metformin-dependent AMPK activation, and to further investigate mTOR dependent 
      and independent signaling pathways driving neuroprotection.
FAU - Demare, Sarah
AU  - Demare S
AD  - Division of Neurodegenerative Disorders, St Boniface Hospital Albrechtsen 
      Research Centre , Winnipeg, MB, Canada.
AD  - Department of Pharmacology and Therapeutics, University of Manitoba , Winnipeg, 
      MB, Canada.
FAU - Kothari, Asha
AU  - Kothari A
AD  - Division of Neurodegenerative Disorders, St Boniface Hospital Albrechtsen 
      Research Centre , Winnipeg, MB, Canada.
AD  - Department of Pharmacology and Therapeutics, University of Manitoba , Winnipeg, 
      MB, Canada.
FAU - Calcutt, Nigel A
AU  - Calcutt NA
AD  - Department of Pathology, University of California San Diego , La Jolla, CA, USA.
FAU - Fernyhough, Paul
AU  - Fernyhough P
AD  - Division of Neurodegenerative Disorders, St Boniface Hospital Albrechtsen 
      Research Centre , Winnipeg, MB, Canada.
AD  - Department of Pharmacology and Therapeutics, University of Manitoba , Winnipeg, 
      MB, Canada.
LA  - eng
GR  - R01 NS081082/NS/NINDS NIH HHS/United States
GR  - MOP-130282/CIHR/Canada
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20201204
PL  - England
TA  - Expert Rev Neurother
JT  - Expert review of neurotherapeutics
JID - 101129944
RN  - 0 (Neuroprotective Agents)
RN  - 9100L32L2N (Metformin)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases
MH  - Animals
MH  - *Diabetes Mellitus, Type 2
MH  - Humans
MH  - *Metformin/therapeutic use
MH  - Neurons
MH  - *Neuroprotective Agents/therapeutic use
PMC - PMC9482886
MID - NIHMS1648228
OTO - NOTNLM
OT  - AMP-activated protein kinase (AMPK)
OT  - PGC-1alpha
OT  - autophagy
OT  - axon regeneration
OT  - diabetes
OT  - mTOR
OT  - mitochondria
OT  - neurodegenerative disease
OT  - neuropathic pain
OT  - neuropathy
COIS- Declaration of interest The authors have no other relevant affiliations or 
      financial involvement with any organization or entity with a financial interest 
      in or conflict with the subject matter or materials discussed in this manuscript 
      apart from those disclosed.
EDAT- 2020/11/10 06:00
MHDA- 2021/12/15 06:00
PMCR- 2022/09/19
CRDT- 2020/11/09 05:21
PHST- 2020/11/10 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2020/11/09 05:21 [entrez]
PHST- 2022/09/19 00:00 [pmc-release]
AID - 10.1080/14737175.2021.1847645 [doi]
PST - ppublish
SO  - Expert Rev Neurother. 2021 Jan;21(1):45-63. doi: 10.1080/14737175.2021.1847645. 
      Epub 2020 Dec 4.