Abstract:
SIGNIFICANCE:Nicotinamide adenine dinucleotide (NAD+) participates in redox reactions and NAD+-dependent signaling processes, which involve the cleavage of NAD+ coupled to posttranslational modifications of proteins or the production of second messengers. Either as a primary cause or as a secondary component of the pathogenic process, mitochondrial dysfunction and oxidative stress are prominent features of several neurodegenerative diseases. Activation of NAD+-dependent signaling pathways has a major effect in the capacity of the cell to modulate mitochondrial function and counteract the deleterious effects of increased oxidative stress. Recent Advances: Progress in the understanding of the biological functions and compartmentalization of NAD+-synthesizing and NAD+-consuming enzymes have led to the emergence of NAD+ metabolism as a major therapeutic target for age-related diseases. CRITICAL ISSUES:Three distinct families of enzymes consume NAD+ as substrate: poly(ADP-ribose) polymerases (PARPs), ADP-ribosyl cyclases (CD38/CD157) and sirtuins. Two main strategies to increase NAD+ availability have arisen. These strategies are based on the utilization of NAD+ intermediates/precursors or the inhibition of the NAD+-consuming enzymes, PARPs and CD38. An increase in endogenous sirtuin activity seems to mediate the protective effect that enhancing NAD+ availability confers in several models of neurodegeneration and age-related diseases. FUTURE DIRECTIONS:A growing body of evidence suggests the beneficial role of enhancing NAD+ availability in models of neurodegeneration. The challenge ahead is to establish the value and safety of the long-term use of these strategies for the treatment of neurodegenerative diseases. Antioxid. Redox Signal. 28, 1652-1668.
journal_name
Antioxid Redox Signaljournal_title
Antioxidants & redox signalingauthors
Pehar M,Harlan BA,Killoy KM,Vargas MRdoi
10.1089/ars.2017.7145subject
Has Abstractpub_date
2018-06-20 00:00:00pages
1652-1668issue
18eissn
1523-0864issn
1557-7716journal_volume
28pub_type
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journal_title:Antioxidants & redox signaling
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journal_title:Antioxidants & redox signaling
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