Mitochondrial dysfunction in Alzheimer's disease: Therapeutic implications of lithium

Neurosci Lett. 2021 Aug 24:760:136078. doi: 10.1016/j.neulet.2021.136078. Epub 2021 Jun 20.

Abstract

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases, characterized by the accumulation of abnormal tau proteins within neurons and amyloid plaques in the brain parenchyma, which leads to progressive loss of neurons in the brain. While the detailed mechanism of the pathogenesis of AD is still unknown, evidence suggests that mitochondrial dysfunction likely plays a fundamental role in the pathogenesis of this disease. Due to the relevance of mitochondrial alterations in AD, recent works have suggested the therapeutic potential of mitochondrial-targeted lithium. Lithium has been shown to possess neuroprotective and neurotrophic properties that could also be related to the upregulation of mitochondrial function. In the current work, we perform a comprehensive investigation of the significance of mitochondrial dysfunction in AD and pharmacological treatment with lithium as imperative in this pathology, through a brief review of the major findings on the effects of lithium as a therapeutic approach targeting mitochondria in the context of AD.

Keywords: Alzheimeŕs disease; Lithium; Mitochondria; Mitochondrial dysfunction; Neuroprotection.

Publication types

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

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / pathology
  • Brain / cytology
  • Brain / drug effects*
  • Brain / pathology
  • Cell Line
  • Clinical Trials as Topic
  • Drug Evaluation, Preclinical
  • Glycogen Synthase Kinase 3 beta / antagonists & inhibitors
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Humans
  • Lithium Compounds / pharmacology
  • Lithium Compounds / therapeutic use*
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Mitochondria / pathology
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism
  • Oxidative Phosphorylation / drug effects
  • Oxidative Stress / drug effects

Substances

  • Lithium Compounds
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta