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.
Conflict of interest statement
Conflicts of interest.
There are no conflicts of interest among any of the authors.
Targeting the prodromal stage of Alzheimer's disease: bioenergetic and mitochondrial opportunities.Neurotherapeutics. 2015 Jan;12(1):66-80. doi: 10.1007/s13311-014-0324-8. Neurotherapeutics. 2015. PMID: 25534394 Free PMC article. Review.
Mitochondrial Dysfunction in Alzheimer's Disease and the Rationale for Bioenergetics Based Therapies.Aging Dis. 2016 Mar 15;7(2):201-14. doi: 10.14336/AD.2015.1007. eCollection 2016 Mar. Aging Dis. 2016. PMID: 27114851 Free PMC article. Review.
Mitochondrial biogenesis: pharmacological approaches.Curr Pharm Des. 2014;20(35):5507-9. doi: 10.2174/138161282035140911142118. Curr Pharm Des. 2014. PMID: 24606795
Oxidative stress induced mitochondrial DNA deletion as a hallmark for the drug development in the context of the cerebrovascular diseases.Recent Pat Cardiovasc Drug Discov. 2011 Sep;6(3):222-41. doi: 10.2174/157489011797376942. Recent Pat Cardiovasc Drug Discov. 2011. PMID: 21906026 Review.
Oxidative stress, mitochondrial dysfunction and cellular stress response in Friedreich's ataxia.J Neurol Sci. 2005 Jun 15;233(1-2):145-62. doi: 10.1016/j.jns.2005.03.012. J Neurol Sci. 2005. PMID: 15896810 Review.
Cited by 1 article
Meta-Analysis of Gene Expression Changes in the Blood of Patients with Mild Cognitive Impairment and Alzheimer's Disease Dementia.Int J Mol Sci. 2019 Oct 30;20(21):5403. doi: 10.3390/ijms20215403. Int J Mol Sci. 2019. PMID: 31671574 Free PMC article.