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CNS Drugs

, Volume 33, Issue 10, pp 957–969 | Cite as

Targeting Mitochondria in Alzheimer Disease: Rationale and Perspectives

  • Chiara Lanzillotta
  • Fabio Di Domenico
  • Marzia Perluigi
  • D. Allan ButterfieldEmail author
Leading Article

Abstract

A decline in mitochondrial function plays a key role in the aging process and increases the incidence of age-related disorders, including Alzheimer disease (AD). Mitochondria—the power station of the organism—can affect several different cellular activities, including abnormal cellular energy generation, response to toxic insults, regulation of metabolism, and execution of cell death. In AD subjects, mitochondria are characterized by impaired function such as lowered oxidative phosphorylation, decreased adenosine triphosphate production, significant increased reactive oxygen species generation, and compromised antioxidant defense. The current review discusses the most relevant mitochondrial defects that are considered to play a significant role in AD and that may offer promising therapeutic targets for the treatment/prevention of AD. In addition, we discuss mechanisms of action and translational potential of some promising mitochondrial and bioenergetic therapeutics for AD including compounds able to potentiate energy production, antioxidants to scavenge reactive oxygen species and reduce oxidative damage, glucose metabolism, and candidates that target mitophagy. While mitochondrial therapeutic strategies have shown promise at the preclinical stage, there has been little progress in clinical trials. Thus, there is an urgent need to better understand the mechanisms regulating mitochondrial homeostasis in order to identify powerful drug candidates that target ‘in and out’ the mitochondria to preserve cognitive functions.

Notes

Compliance with Ethical Standards

Funding

This work was supported in part by NIH Grants to DAB [AG060056; AG055596-01A1].

Conflict of interest

There are no conflicts of interest among any of the authors.

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Biochemical SciencesSapienza University of RomeRomeItaly
  2. 2.Department of ChemistryUniversity of KentuckyLexingtonUSA
  3. 3.Sanders-Brown Center on AgingUniversity of KentuckyLexingtonUSA

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