Targeting Mitophagy in Alzheimer’s Disease

Article type: Review Article

Authors: Jayatunga, Dona P.W.^a | Hone, Eugene^{a; b} | Bharadwaj, Prashant^{a; b} | Garg, Manohar^{c; d} | Verdile, Giuseppe^{a; e} | Guillemin, Gilles J.^{f; g} | Martins, Ralph N.^{a; h; i; j; k; *}

Affiliations: [a] Centre of Excellence for Alzheimer’s Disease Research & Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia | [b] Cooperative Research Centre for Mental Health, Carlton, VIC, Australia | [c] School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, Australia | [d] Riddet Institute, Massey University, Palmerston North, New Zealand | [e] School of Pharmacy and Biomedical Sciences, Faculty of Health Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia | [f] Department of Pharmacology, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia | [g] St. Vincent’s Centre for Applied Medical Research, Sydney, NSW, Australia | [h] Australian Alzheimer’s Research Foundation, Ralph and Patricia Sarich Neuroscience Research Institute, Nedlands, WA, Australia | [i] Department of Biomedical Sciences, Macquarie University, Sydney, NSW, Australia | [j] School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, WA, Australia | [k] KaRa Institute of Neurological Diseases, Sydney, NSW, Australia

Correspondence: [*] Correspondence to: Professor Ralph N. Martins, School of Medical and Health Sciences, Edith Cowan University, 270 Joondalup Drive, Joondalup, Western Australia, 6027 Australia. Tel.: +61 8 9347 4200; Fax: +61 8 9347 4299; E-mail: [email protected].

Abstract: Mitochondria perform many essential cellular functions including energy production, calcium homeostasis, transduction of metabolic and stress signals, and mediating cell survival and death. Maintaining viable populations of mitochondria is therefore critical for normal cell function. The selective disposal of damaged mitochondria, by a pathway known as mitophagy, plays a key role in preserving mitochondrial integrity and quality. Mitophagy reduces the formation of reactive oxygen species and is considered as a protective cellular process. Mitochondrial dysfunction and deficits of mitophagy have important roles in aging and especially in neurodegenerative disorders such as Alzheimer’s disease (AD). Targeting mitophagy pathways has been suggested to have potential therapeutic effects against AD. In this review, we aim to briefly discuss the emerging concepts on mitophagy, molecular regulation of the mitophagy process, current mitophagy detection methods, and mitophagy dysfunction in AD. Finally, we will also briefly examine the stimulation of mitophagy as an approach for attenuating neurodegeneration in AD.

Keywords: Alzheimer’s disease, mitophagy, neuroprotection, nutraceuticals

DOI: 10.3233/JAD-191258

Journal: Journal of Alzheimer's Disease, vol. 78, no. 4, pp. 1273-1297, 2020