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Antioxidant Modulation of mTOR and Sirtuin Pathways in Age-Related Neurodegenerative Diseases

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Abstract

In the human body, cell division and metabolism are expected to transpire uneventfully for approximately 25 years. Then, secondary metabolism and cell damage products accumulate, and ageing phenotypes are acquired, causing the progression of disease. Among these age-related diseases, neurodegenerative diseases have attracted considerable attention because of their irreversibility, the absence of effective treatment and their relationship with social and economic pressures. Mechanistic (formerly mammalian) target of rapamycin (mTOR), sirtuin (SIRT) and insulin/insulin growth factor 1 (IGF1) signalling pathways are among the most important pathways in ageing-associated conditions, such as neurodegeneration. These longevity-related pathways are associated with a diversity of various processes, including metabolism, cognition, stress reaction and brain plasticity. In this review, we discuss the roles of sirtuin and mTOR in ageing and neurodegeneration, with an emphasis on their regulation of autophagy, apoptosis and mitochondrial energy metabolism. The intervention of neurodegeneration using potential antioxidants, including vitamins, phytochemicals, resveratrol, herbals, curcumin, coenzyme Q10 and minerals, specifically aimed at retaining mitochondrial function in the treatment of Alzheimer’s disease, Parkinson’s disease and Huntington’s disease is highlighted.

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Acknowledgements

This review is part of a research study financially supported by the Ministry of Higher Education Grant (FRGS/1/2019/SKK08/UKM/01/4).

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  1. Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Level 17, Preclinical Building, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000, Kuala Lumpur, Malaysia

    Asmaa Abdullah, Nuraqila Mohd Murshid & Suzana Makpol

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SM developed the concept and revised the manuscript. AA and NMM analysed the literature and wrote and edited the draft of the manuscript. NMM drew the diagrams and prepared the table.

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Correspondence to Suzana Makpol.

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Abdullah, A., Mohd Murshid, N. & Makpol, S. Antioxidant Modulation of mTOR and Sirtuin Pathways in Age-Related Neurodegenerative Diseases. Mol Neurobiol 57, 5193–5207 (2020). https://doi.org/10.1007/s12035-020-02083-1

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