The Gut-Brain Axis in Alzheimer's and Parkinson's Diseases: The Catalytic Role of Mitochondria

J Alzheimers Dis. 2024;100(2):413-429. doi: 10.3233/JAD-240524.

Abstract

Accumulating evidence suggests that gut inflammation is implicated in neuroinflammation in Alzheimer's and Parkinson's diseases. Despite the numerous connections it remains unclear how the gut and the brain communicate and whether gut dysbiosis is the cause or consequence of these pathologies. Importantly, several reports highlight the importance of mitochondria in the gut-brain axis, as well as in mechanisms like gut epithelium self-renewal, differentiation, and homeostasis. Herein we comprehensively address the important role of mitochondria as a cellular hub in infection and inflammation and as a link between inflammation and neurodegeneration in the gut-brain axis. The role of mitochondria in gut homeostasis and as well the crosstalk between mitochondria and gut microbiota is discussed. Significantly, we also review studies highlighting how gut microbiota can ultimately affect the central nervous system. Overall, this review summarizes novel findings regarding this cross-talk where the mitochondria has a main role in the pathophysiology of both Alzheimer's and Parkinson's disease strengthen by cellular, animal and clinical studies.

Keywords: Alzheimer’s disease; Parkinson’s disease; gut microbiome metabolites; gut-brain axis; inflammation; mitochondria.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease* / metabolism
  • Alzheimer Disease* / pathology
  • Animals
  • Brain / metabolism
  • Brain-Gut Axis* / physiology
  • Dysbiosis
  • Gastrointestinal Microbiome* / physiology
  • Humans
  • Mitochondria* / metabolism
  • Parkinson Disease* / metabolism
  • Parkinson Disease* / pathology