Resveratrol Mediated Regulation of Hippocampal Neuroregenerative Plasticity via SIRT1 Pathway in Synergy with Wnt Signaling: Neurotherapeutic Implications to Mitigate Memory Loss in Alzheimer’s Disease

Article type: Review Article

Authors: Surya, Kumar^a | Manickam, Nivethitha^{b; 1} | Jayachandran, Kesavan Swaminathan^c | Kandasamy, Mahesh^{b; d; *} | Anusuyadevi, Muthuswamy^{a; *}

Affiliations: [a] Department of Biochemistry, Molecular Neuro-gerontology Laboratory, School of Life Sciences, Bharathidasan University, Tiruchirappalli, Tamil Nadu, India | [b] Department of Animal Science, Laboratory of Stem Cells and Neuroregeneration, School of Life Sciences, Bharathidasan University, Tiruchirappalli, Tamil Nadu, India | [c] Department of Bioinformatics, Molecular Cardiology and Drug Discovery Laboratory, School of Life Sciences, Bharathidasan University, Tiruchirappalli, Tamil Nadu, India | [d] University Grants Commission-Faculty Recharge Programme (UGC-FRP), New Delhi, India

Correspondence: [*] Correspondence to: Dr. Muthuswamy Anusuyadevi, Associate Professor, Molecular Neuro-Gerontology Laboratory, Department of Biochemistry, School of Life Sciences, Bharathidasan University, Tiruchirappalli-620024, India. Tel.: +9498036529; E-mail: [email protected] and Dr. Mahesh Kandasamy, UGC-Assistant Professor, Laboratory of Stem Cells and Neuroregeneration, Department of Animal Science, School of Life Sciences, Bharathidasan University, Tiruchirappalli-620024, India. Tel.: +91 431 2407040; E-mails: [email protected], [email protected].

Note: [1] Present address: Institute for Cardiovascular Regeneration, Goethe University, Frankfurt am Main, Germany.

Abstract: Alzheimer’s disease (AD) is a major form of dementia. Abnormal amyloidogenic event-mediated degeneration of cholinergic neurons in the cognitive centers of the brain has been attributed to neuropathological sequelae and behavioral deficits in AD. Besides, impaired adult neurogenesis in the hippocampus has experimentally been realized as an underlying cause of dementia regardless of neurodegeneration. Therefore, nourishing the neurogenic process in the hippocampus has been considered an effective therapeutic strategy to mitigate memory loss. In the physiological state, the Wnt pathway has been identified as a potent mitogenic generator in the hippocampal stem cell niche. However, downstream components of Wnt signaling have been noticed to be downregulated in AD brains. Resveratrol (RSV) is a potent Sirtuin1 (SIRT1) enhancer that facilitates neuroprotection and promotes neurogenesis in the hippocampus of the adult brain. While SIRT1 is an important positive regulator of Wnt signaling, ample reports indicate that RSV treatment strongly mediates the fate determination of stem cells through Wnt signaling. However, the possible therapeutic roles of RSV-mediated SIRT1 enhancement on the regulation of hippocampal neurogenesis and reversal of memory loss through the Wnt signaling pathway have not been addressed yet. Taken together, this review describes RSV-mediated effects on the regulation of hippocampal neurogenesis via the activation of SIRT1 in synergy with the Wnt signaling. Further, the article emphasizes a hypothesis that RSV treatment can provoke the activation of quiescent neural stem cells and prime their neurogenic capacity in the hippocampus via Wnt signaling in AD.

Keywords: Adult neurogenesis, Alzheimer’s disease, cell cycle, hippocampus, resveratrol, Sirtuin1, Wnt pathway

DOI: 10.3233/JAD-220559

Journal: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-17, 2022