TY - JOUR
T1 - NAD+ homeostasis in human health and disease
AU - Zapata-Pérez, Rubén
AU - Wanders, Ronald J. A.
AU - van Karnebeek, Clara D. M.
AU - Houtkooper, Riekelt H.
N1 - Funding Information: RZ‐P was supported by a postdoctoral grant from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska‐Curie grant agreement number 840110. Work in the Houtkooper group is financially supported by an ERC Starting grant (no. 638290) and a VIDI grant from ZonMw (no. 91715305). Publisher Copyright: © 2021 The Authors. Published under the terms of the CC BY 4.0 license
PY - 2021/7/7
Y1 - 2021/7/7
N2 - Depletion of nicotinamide adenine dinucleotide (NAD+), a central redox cofactor and the substrate of key metabolic enzymes, is the causative factor of a number of inherited and acquired diseases in humans. Primary deficiencies of NAD+ homeostasis are the result of impaired biosynthesis, while secondary deficiencies can arise due to other factors affecting NAD+ homeostasis, such as increased NAD+ consumption or dietary deficiency of its vitamin B3 precursors. NAD+ depletion can manifest in a wide variety of pathological phenotypes, ranging from rare inherited defects, characterized by congenital malformations, retinal degeneration, and/or encephalopathy, to more common multifactorial, often age-related, diseases. Here, we discuss NAD+ biochemistry and metabolism and provide an overview of the etiology and pathological consequences of alterations of the NAD+ metabolism in humans. Finally, we discuss the state of the art of the potential therapeutic implications of NAD+ repletion for boosting health as well as treating rare and common diseases, and the possibilities to achieve this by means of the different NAD+-enhancing agents.
AB - Depletion of nicotinamide adenine dinucleotide (NAD+), a central redox cofactor and the substrate of key metabolic enzymes, is the causative factor of a number of inherited and acquired diseases in humans. Primary deficiencies of NAD+ homeostasis are the result of impaired biosynthesis, while secondary deficiencies can arise due to other factors affecting NAD+ homeostasis, such as increased NAD+ consumption or dietary deficiency of its vitamin B3 precursors. NAD+ depletion can manifest in a wide variety of pathological phenotypes, ranging from rare inherited defects, characterized by congenital malformations, retinal degeneration, and/or encephalopathy, to more common multifactorial, often age-related, diseases. Here, we discuss NAD+ biochemistry and metabolism and provide an overview of the etiology and pathological consequences of alterations of the NAD+ metabolism in humans. Finally, we discuss the state of the art of the potential therapeutic implications of NAD+ repletion for boosting health as well as treating rare and common diseases, and the possibilities to achieve this by means of the different NAD+-enhancing agents.
KW - NAD
KW - NAD homeostasis
KW - disease
KW - metabolism
KW - therapy
UR - http://www.scopus.com/inward/record.url?scp=85106586548&partnerID=8YFLogxK
U2 - https://doi.org/10.15252/emmm.202113943
DO - https://doi.org/10.15252/emmm.202113943
M3 - Review article
C2 - 34041853
SN - 1757-4676
VL - 13
JO - EMBO molecular medicine
JF - EMBO molecular medicine
IS - 7
M1 - e13943
ER -