Emerging neuroprotective effect of metformin in Parkinson's disease: A molecular crosstalk

Yam Nath Paudel, Efthalia Angelopoulou, Christina Piperi, Mohd Farooq Shaikh, Iekhsan Othman

Research output: Contribution to journalReview ArticleResearchpeer-review

11 Citations (Scopus)

Abstract

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 α-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.

Original languageEnglish
Article number104593
Number of pages13
JournalPharmacological Research
Volume152
DOIs
Publication statusPublished - Feb 2020

Keywords

  • Autophagy
  • Metformin
  • Neurodegeneration
  • Neuroinflammation
  • Neuroprotection
  • Parkinson's disease

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