PMID- 31843673
OWN - NLM
STAT- MEDLINE
DCOM- 20201231
LR  - 20201231
IS  - 1096-1186 (Electronic)
IS  - 1043-6618 (Linking)
VI  - 152
DP  - 2020 Feb
TI  - Emerging neuroprotective effect of metformin in Parkinson's disease: A molecular 
      crosstalk.
PG  - 104593
LID - S1043-6618(19)31779-7 [pii]
LID - 10.1016/j.phrs.2019.104593 [doi]
AB  - Parkinson's disease (PD) is a devastating neurodegenerative disorder 
      characterized by the progressive loss of dopaminergic neurons in the substantia 
      nigra pars compacta (SNpc) and Lewy pathology. PD is a major concern of today's 
      aging population and has emerged as a global health burden. Despite the rapid 
      advances in PD research over the past decades, the gold standard therapy provides 
      only symptomatic relief and fails to halt disease progression. Therefore, 
      exploring novel disease-modifying therapeutic strategies is highly demanded. 
      Metformin, which is currently used as a first-line therapy for type 2 diabetes 
      mellitus (T2DM), has recently demonstrated to exert a neuroprotective role in 
      several neurodegenerative disorders including PD, both in vitro and in vivo. In 
      this review, we explore the neuroprotective potential of metformin based on 
      emerging evidence from pre-clinical and clinical studies. Regarding the 
      underlying molecular mechanisms, metformin has been shown to inhibit alpha-synuclein 
      (SNCA) phosphorylation and aggregation, prevent mitochondrial dysfunction, 
      attenuate oxidative stress, modulate autophagy mainly via AMP-activated protein 
      kinase (AMPK) activation, as well as prevent neurodegeneration and 
      neuroinflammation. Overall, the neuroprotective effects of metformin in PD 
      pathogenesis present a novel promising therapeutic strategy that might overcome 
      the limitations of current PD treatment.
CI  - Copyright (c) 2019 Elsevier Ltd. All rights reserved.
FAU - Paudel, Yam Nath
AU  - Paudel YN
AD  - Neuropharmacology Research Laboratory, Jeffrey Cheah School of Medicine and 
      Health Sciences, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia. 
      Electronic address: yam.paudel@monash.edu.
FAU - Angelopoulou, Efthalia
AU  - Angelopoulou E
AD  - Department of Biological Chemistry, Medical School, National and Kapodistrian 
      University of Athens, Athens, Greece. Electronic address: angelthal@med.uoa.gr.
FAU - Piperi, Christina
AU  - Piperi C
AD  - Department of Biological Chemistry, Medical School, National and Kapodistrian 
      University of Athens, Athens, Greece. Electronic address: cpiperi@med.uoa.gr.
FAU - Shaikh, Mohd Farooq
AU  - Shaikh MF
AD  - Neuropharmacology Research Laboratory, Jeffrey Cheah School of Medicine and 
      Health Sciences, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia. 
      Electronic address: Farooq.shaikh@monash.edu.
FAU - Othman, Iekhsan
AU  - Othman I
AD  - Neuropharmacology Research Laboratory, Jeffrey Cheah School of Medicine and 
      Health Sciences, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia. 
      Electronic address: iekhsan.othman@monash.edu.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20191213
PL  - Netherlands
TA  - Pharmacol Res
JT  - Pharmacological research
JID - 8907422
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Neuroprotective Agents)
RN  - 9100L32L2N (Metformin)
SB  - IM
MH  - Animals
MH  - Autophagy/drug effects
MH  - Behavior, Animal/drug effects
MH  - Dopaminergic Neurons/drug effects
MH  - Encephalitis/drug therapy
MH  - Humans
MH  - Hypoglycemic Agents/*therapeutic use
MH  - Metformin/*therapeutic use
MH  - Mitochondria/drug effects
MH  - Neuroprotective Agents/*therapeutic use
MH  - Parkinson Disease/*drug therapy
OTO - NOTNLM
OT  - Autophagy
OT  - Metformin
OT  - Neurodegeneration
OT  - Neuroinflammation
OT  - Neuroprotection
OT  - Parkinson's disease
COIS- Declaration of Competing Interest All the authors declare no potential conflict 
      of interest.
EDAT- 2019/12/18 06:00
MHDA- 2021/01/01 06:00
CRDT- 2019/12/18 06:00
PHST- 2019/08/22 00:00 [received]
PHST- 2019/11/20 00:00 [revised]
PHST- 2019/12/11 00:00 [accepted]
PHST- 2019/12/18 06:00 [pubmed]
PHST- 2021/01/01 06:00 [medline]
PHST- 2019/12/18 06:00 [entrez]
AID - S1043-6618(19)31779-7 [pii]
AID - 10.1016/j.phrs.2019.104593 [doi]
PST - ppublish
SO  - Pharmacol Res. 2020 Feb;152:104593. doi: 10.1016/j.phrs.2019.104593. Epub 2019 
      Dec 13.