The Role of Mitochondrial Dysfunction in the Progression of Alzheimer's Disease

Curr Med Chem. 2018;25(40):5578-5587. doi: 10.2174/0929867324666170616110111.

Abstract

The current molecular understanding of Alzheimer's disease (AD) has still not resulted in successful interventions. Mitochondrial dysfunction of the AD brain is currently emerging as a hallmark of this disease. One mitochondrial function often affected in AD is oxidative phosphorylation responsible for ATP production, but also for production of reactive oxygen species (ROS) and for the de novo synthesis of pyrimidines. This paper reviews the role of mitochondrial produced ROS and pyrimidines in the aetiology of AD and their proposed role in oxidative degeneration of macromolecules, synthesis of essential phospholipids and maintenance of mitochondrial viability in the AD brain.

Keywords: Brain; DNA repair; Mitochondria; Nucleotide metabolism; dNTP pools..

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology*
  • Animals
  • Humans
  • Mitochondria / metabolism*
  • Mitochondria / pathology*
  • Phospholipids / biosynthesis
  • Phospholipids / chemistry
  • Pyrimidines / biosynthesis
  • Pyrimidines / chemistry
  • Reactive Oxygen Species / metabolism

Substances

  • Phospholipids
  • Pyrimidines
  • Reactive Oxygen Species