Role of Sirtuins in Modulating Neurodegeneration of the Enteric Nervous System and Central Nervous System

• Type of Material: Article
• Authors: Pavithra Chandramowlishwaran, Emory University; Anitha Vijay, Pennsylvania State University; Daniel Abraham, Thomas Jefferson University; Ge Li, Emory University; Simon Mwangi, Emory University; Shanthi Srinivasan, Emory University
• Language: English
• Date: 2020-12-22
• Publisher: FRONTIERS MEDIA SA
• Publication Version: Final Published Version
• Copyright Statement: © 2020 Chandramowlishwaran, Vijay, Abraham, Li, Mwangi and Srinivasan.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3389/fnins.2020.614331
• Title of Journal or Parent Work: FRONTIERS IN NEUROSCIENCE
• Volume: 14
• Start Page: 614331
• End Page: 614331
• Grant/Funding Information: This work was supported by U.S. National Institutes of Health (NIH) grants R01DK080684 (SS) and VA Research and Development Merit Review Award # BX000136-12 (SS).
• Keywords: MELANOCORTIN SYSTEM; MYENTERIC PLEXUS; OXIDATIVE STRESS; neuronal survival; INSULIN-RESISTANCE; sirtuin (SIRT); CHAIN FATTY-ACIDS; Life Sciences & Biomedicine; central nervous system; enteric nervous system; GUT MICROBIOTA; Science & Technology; Neurosciences; GLUCOSE-HOMEOSTASIS; Neurosciences & Neurology; ALZHEIMERS-DISEASE; BARRIER DYSFUNCTION; BETA PROTEIN-PRECURSOR; myenteric plexus; gut microbiota; neurodegeneration
• Research Categories: Biology, Neuroscience; Biology, General

Abstract

Neurodegeneration of the central and enteric nervous systems is a common feature of aging and aging-related diseases, and is accelerated in individuals with metabolic dysfunction including obesity and diabetes. The molecular mechanisms of neurodegeneration in both the CNS and ENS are overlapping. Sirtuins are an important family of histone deacetylases that are important for genome stability, cellular response to stress, and nutrient and hormone sensing. They are activated by calorie restriction (CR) and by the coenzyme, nicotinamide adenine dinucleotide (NAD+). Sirtuins, specifically the nuclear SIRT1 and mitochondrial SIRT3, have been shown to have predominantly neuroprotective roles in the CNS while the cytoplasmic sirtuin, SIRT2 is largely associated with neurodegeneration. A systematic study of sirtuins in the ENS and their effect on enteric neuronal growth and survival has not been conducted. Recent studies, however, also link sirtuins with important hormones such as leptin, ghrelin, melatonin, and serotonin which influence many important processes including satiety, mood, circadian rhythm, and gut homeostasis. In this review, we address emerging roles of sirtuins in modulating the metabolic challenges from aging, obesity, and diabetes that lead to neurodegeneration in the ENS and CNS. We also highlight a novel role for sirtuins along the microbiota-gut-brain axis in modulating neurodegeneration.