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© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Mitochondrial dysfunction including deficits of mitophagy is seen in aging and neurodegenerative disorders including Alzheimer’s disease (AD). Apart from traditionally targeting amyloid beta (Aβ), the main culprit in AD brains, other approaches include investigating impaired mitochondrial pathways for potential therapeutic benefits against AD. Thus, a future therapy for AD may focus on novel candidates that enhance optimal mitochondrial integrity and turnover. Bioactive food components, known as nutraceuticals, may serve as such agents to combat AD. Urolithin A is an intestinal microbe-derived metabolite of a class of polyphenols, ellagitannins (ETs). Urolithin A is known to exert many health benefits. Its antioxidant, anti-inflammatory, anti-atherogenic, anti-Aβ, and pro-mitophagy properties are increasingly recognized. However, the underlying mechanisms of urolithin A in inducing mitophagy is poorly understood. This review discusses the mitophagy deficits in AD and examines potential molecular mechanisms of its activation. Moreover, the current knowledge of urolithin A is discussed, focusing on its neuroprotective properties and its potential to induce mitophagy. Specifically, this review proposes potential mechanisms by which urolithin A may activate and promote mitophagy.

Details

Title
Therapeutic Potential of Mitophagy-Inducing Microflora Metabolite, Urolithin A for Alzheimer’s Disease
Author
Dona Pamoda W Jayatunga 1   VIAFID ORCID Logo  ; Hone, Eugene 2 ; Khaira, Harjot 3 ; Lunelli, Taciana 3 ; Singh, Harjinder 3 ; Guillemin, Gilles J 4 ; Binosha Fernando 1 ; Garg, Manohar L 5   VIAFID ORCID Logo  ; Verdile, Giuseppe 6 ; Martins, Ralph N 7 

 Centre of Excellence for Alzheimer’s Disease Research & Care, School of Medical and Health Sciences, Edith Cowan University, 270 Joondalup Drive, Joondalup, WA 6027, Australia; [email protected] (D.P.W.J.); [email protected] (E.H.); [email protected] (B.F.); [email protected] (G.V.) 
 Centre of Excellence for Alzheimer’s Disease Research & Care, School of Medical and Health Sciences, Edith Cowan University, 270 Joondalup Drive, Joondalup, WA 6027, Australia; [email protected] (D.P.W.J.); [email protected] (E.H.); [email protected] (B.F.); [email protected] (G.V.); Cooperative Research Centre for Mental Health, Carlton, VIC 3053, Australia 
 Riddet Institute, Massey University, Private Bag 11222, Palmerston North 4442, New Zealand; [email protected] (H.K.); [email protected] (T.L.); [email protected] (H.S.); [email protected] (M.L.G.) 
 Department of Pharmacology, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia; [email protected]; St. Vincent’s Centre for Applied Medical Research, Sydney, NSW 2011, Australia 
 Riddet Institute, Massey University, Private Bag 11222, Palmerston North 4442, New Zealand; [email protected] (H.K.); [email protected] (T.L.); [email protected] (H.S.); [email protected] (M.L.G.); School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW 2308, Australia 
 Centre of Excellence for Alzheimer’s Disease Research & Care, School of Medical and Health Sciences, Edith Cowan University, 270 Joondalup Drive, Joondalup, WA 6027, Australia; [email protected] (D.P.W.J.); [email protected] (E.H.); [email protected] (B.F.); [email protected] (G.V.); School of Pharmacy and Biomedical Sciences, Faculty of Health Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, WA 6102, Australia 
 Centre of Excellence for Alzheimer’s Disease Research & Care, School of Medical and Health Sciences, Edith Cowan University, 270 Joondalup Drive, Joondalup, WA 6027, Australia; [email protected] (D.P.W.J.); [email protected] (E.H.); [email protected] (B.F.); [email protected] (G.V.); Australian Alzheimer’s Research Foundation, Ralph and Patricia Sarich Neuroscience Research Institute, 8 Verdun Street., Nedlands, WA 6009, Australia; Department of Biomedical Sciences, Macquarie University, Sydney, NSW 2109, Australia 
First page
3744
Publication year
2021
Publication date
2021
Publisher
MDPI AG
e-ISSN
20726643
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2602147154
Copyright
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.