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. 2012 Oct 15;199(2):205-9.
doi: 10.1083/jcb.201207019.

Exploring the therapeutic space around NAD+

Riekelt H Houtkooper  1 , Johan Auwerx
Affiliations

Exploring the therapeutic space around NAD+

Riekelt H Houtkooper et al. J Cell Biol. .

Abstract

NAD(+) is a central metabolite in the cell. Changes in NAD(+) abundance and the activity of NAD(+)-dependent enzymes, such as the sirtuins, are at the core of metabolic/mitochondrial diseases, such as obesity and diabetes, and of cancer and neurodegeneration. Here, we discuss how maintaining or raising NAD(+) levels can improve metabolism and prevent age-related functional decline and associated disease, and how basic scientific discoveries in the NAD(+) signaling pathway are being translated to the clinic.

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Figures

Figure 1.
Figure 1.
Diverse metabolic actions of NAD+. Schematic overview of how NAD+ and NADH are used as metabolic cofactors, either in more traditional oxidoreductase reactions (green NAD+) or in more recently discovered regulatory roles as a cosubstrate for the reactions catalyzed by sirtuins and PARPs (red NAD+). Note: reactions shown here are only a small representation of those that involve NAD+.
Figure 2.
Figure 2.
Metabolic control by modulating NAD+ levels. (A) NAD+ levels dictate the activity of SIRT1 and SIRT3, which in turn regulate a variety of metabolic proteins. The protein targets shown here just represent a selection. (B) Mitochondrial function is regulated by sirtuin enzymes, notably SIRT1 and SIRT3, which are under the control of NAD+ levels. Modulating NAD+ levels results in improved mitochondrial function with clinically beneficial effects.
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