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NAD + in Brain Aging and Neurodegenerative Disorders

Authors
  • Lautrup, Sofie1
  • Sinclair, David A.2, 3
  • Mattson, Mark P.4
  • Fang, Evandro F.1, 5
  • 1 Department of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, 1478 Lørenskog, Norway
  • 2 Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
  • 3 Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia
  • 4 Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
  • 5 The Norwegian Centre on Healthy Ageing (NO-Age), Oslo, Norway
Type
Published Article
Journal
Cell metabolism
Publication Date
Oct 01, 2019
Volume
30
Issue
4
Pages
630–655
Identifiers
DOI: 10.1016/j.cmet.2019.09.001
PMID: 31577933
PMCID: PMC6787556
Source
PubMed Central
License
Unknown

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.

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