NAD+ in Brain Aging and Neurodegenerative Disorders
Sofie Lautrup, David A Sinclair, Mark P Mattson, Evandro F Fang, Sofie Lautrup, David A Sinclair, Mark P Mattson, Evandro F Fang
Abstract
NAD+ is a pivotal metabolite involved in cellular bioenergetics, genomic stability, mitochondrial homeostasis, adaptive stress responses, and cell survival. Multiple NAD+-dependent enzymes are involved in synaptic plasticity and neuronal stress resistance. Here, we review emerging findings that reveal key roles for NAD+ and related metabolites in the adaptation of neurons to a wide range of physiological stressors and in counteracting processes in neurodegenerative diseases, such as those occurring in Alzheimer's, Parkinson's, and Huntington diseases, and amyotrophic lateral sclerosis. Advances in understanding the molecular and cellular mechanisms of NAD+-based neuronal resilience will lead to novel approaches for facilitating healthy brain aging and for the treatment of a range of neurological disorders.
Keywords: Alzheimer’s disease; NAD+; Parkinson’s disease; brain aging; mitochondria; mitophagy; neurodegeneration; neuronal plasticity; sirtuins.
Conflict of interest statement
DECLARATION OF INTERESTS
E.F.F. is a visiting professor at the First Affiliated Hospital, Sun Yat-Sen University (Guangzhou, China), a Guest Professor at School of Medicine, Jinan University (Guangzhou, China), and a Visiting Professor at the Department of Clinical Gerontology, the First Affiliated Hospital, Zhengzhou University (Zhengzhou, China). E.F.F. has CRADA arrangements with ChromaDex and is a consultant to Aladdin Healthcare Technologies and the Vancouver Dementia Prevention Centre. D.A.S. is a founder, equity owner, board member, advisor to, director of, consultant to, investor in, and/or inventor on patents licensed to Vium, Jupiter Orphan Therapeutics, Cohbar, Galilei Biosciences, GlaxoSmithKline, OvaScience, EMD Millipore, Wellomics, Inside Tracker, Caudalie, Bayer Crop Science, Longwood Fund, Zymo Research, EdenRoc Sciences (and affiliates Arc-Bio, Dovetail Genomics, Claret Bioscience, Revere Biosensors, UpRNA and MetroBiotech [an NAD booster company], and Liberty Biosecurity), and Life Biosciences (and affiliates Selphagy, Senolytic Therapeutics, Spotlight Biosciences, Animal Biosciences, Iduna, Immetas, Prana, Continuum Biosciences, Jumpstart Fertility [an NAD booster company], and Lua Communications). D.A.S. sits on the board of directors of both companies. D.A.S. is an inventor on a patent application filed by Mayo Clinic and Harvard Medical School that has been licensed to Elysium Health; his personal royalty share is directed to the Sinclair lab. For more information, see https://genetics.med.harvard.edu/sinclair-test/people/sinclair-other.php.
Copyright © 2019 Elsevier Inc. All rights reserved.
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Source: PubMed