Therapeutic potential of mitophagy-inducing microflora metabolite, urolithin A for alzheimer’s disease

Dona Pamoda W. Jayatunga, Eugene Hone, Harjot Khaira, Taciana Lunelli, Harjinder Singh, Gilles J. Guillemin, Binosha Fernando, Manohar L. Garg, Giuseppe Verdile, Ralph N. Martins*

*Corresponding author for this work

    Research output: Contribution to journalReview articlepeer-review

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    Abstract

    Mitochondrial dysfunction including deficits of mitophagy is seen in aging and neuro-degenerative 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. Bi-oactive food components, known as nutraceuticals, may serve as such agents to combat AD. Uro-lithin 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-athero-genic, anti-Aβ, and pro-mitophagy properties are increasingly recognized. However, the underly-ing 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. More-over, 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.

    Original languageEnglish
    Article number3744
    Pages (from-to)1-22
    Number of pages22
    JournalNutrients
    Volume13
    Issue number11
    Early online date23 Oct 2021
    DOIs
    Publication statusPublished - Nov 2021

    Bibliographical note

    Copyright the Author(s) 2021. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

    Keywords

    • Alzheimer’s disease
    • Mitophagy
    • Neuroprotection
    • Nutraceuticals
    • Pomegranate
    • Urolithin A

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