Highlighting the Protective or Degenerative Role of AMPK Activators in Dementia Experimental Models

CNS Neurol Disord Drug Targets. 2021;20(9):786-801. doi: 10.2174/1871527320666210526160214.

Abstract

AMP-activated protein kinase (AMPK) is a serine/threonine kinase and a driving or deterrent factor in the development of neurodegenerative diseases and dementia. AMPK affects intracellular proteins like the mammalian target of rapamycin (mTOR) Peroxisome proliferator-activated receptor-γ coactivator 1-α (among others) contributes to a wide range of intracellular activities based on its downstream molecules such as energy balancing (ATP synthesis), extracellular inflammation, cell growth, and neuronal cell death (such as apoptosis, necrosis, and necroptosis). Several studies have looked at the dual role of AMPK in neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), and Huntington disease (HD) but the exact effect of this enzyme on dementia, stroke, and motor neuron dysfunction disorders has not been elucidated yet. In this article, we review current research on the effects of AMPK on the brain to give an overview of the relationship. More specifically, we review the neuroprotective or neurodegenerative effects of AMPK or AMPK activators like metformin, resveratrol, and 5-aminoimidazole-4-carboxamide- 1-β-d-ribofuranoside on neurological diseases and dementia, which exert through the intracellular molecules involved in neuronal survival or death.

Keywords: AMPK; AMPK activators.; brain; dementia; neurodegenerative disease; neuroprotective.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Aminoimidazole Carboxamide / pharmacology
  • Animals
  • Dementia / metabolism*
  • Humans
  • Models, Theoretical*
  • Neurons / metabolism
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Resveratrol / pharmacology
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • PPARGC1A protein, human
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Aminoimidazole Carboxamide
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • AMP-Activated Protein Kinases
  • Resveratrol