Mitochondrial Dysfunction and Parkinson's Disease: Pathogenesis and Therapeutic Strategies

Neurochem Res. 2023 Aug;48(8):2285-2308. doi: 10.1007/s11064-023-03904-0. Epub 2023 Mar 21.

Abstract

Parkinson's disease (PD) is a common age-related neurodegenerative disorder whose pathogenesis is not completely understood. Mitochondrial dysfunction and increased oxidative stress have been considered as major causes and central events responsible for the progressive degeneration of dopaminergic (DA) neurons in PD. Therefore, investigating mitochondrial disorders plays a role in understanding the pathogenesis of PD and can be an important therapeutic target for this disease. This study discusses the effect of environmental, genetic and biological factors on mitochondrial dysfunction and also focuses on the mitochondrial molecular mechanisms underlying neurodegeneration, and its possible therapeutic targets in PD, including reactive oxygen species generation, calcium overload, inflammasome activation, apoptosis, mitophagy, mitochondrial biogenesis, and mitochondrial dynamics. Other potential therapeutic strategies such as mitochondrial transfer/transplantation, targeting microRNAs, using stem cells, photobiomodulation, diet, and exercise were also discussed in this review, which may provide valuable insights into clinical aspects. A better understanding of the roles of mitochondria in the pathophysiology of PD may provide a rationale for designing novel therapeutic interventions in our fight against PD.

Keywords: Mitochondrial biogenesis; Mitochondrial dynamics; Mitochondrial dysfunction; Mitochondrial transplantation; Parkinson’s disease.

Publication types

  • Review

MeSH terms

  • Dopaminergic Neurons / metabolism
  • Humans
  • Mitochondria / metabolism
  • Mitochondrial Diseases* / pathology
  • Oxidative Stress / physiology
  • Parkinson Disease* / metabolism