Front Biosci. 2006 Sep 1;11:3129-48.

NAD+ and NADH in cellular functions and cell death.


Ying W.


Department of Neurology, University of California, San Francisco
Veterans Affairs Medical Center,


San Francisco, CA 94121, USA. Weihai.Ying@@@@ucsf.edu


Increasing evidence has indicated that NAD+ and NADH play critical
roles not only in energy metabolism, but also in cell death and
various cellular functions including regulation of calcium homeostasis
and gene expression. It has also been indicated that NAD+ and NADH are
mediators of multiple major biological processes including aging. NAD+
and NADH produce the biological effects by regulating numerous NAD+/
NADH-dependent enzymes, including dehydrogenases, poly(ADP-ribose)
polymerases, Sir2 family proteins (sirtuins), mono(ADP-
ribosyl)transferases, and ADP-ribosyl cyclases. Of particular
interest, NAD+-dependent generation of ADP-ribose, cyclic ADP-ribose
and O-acetyl-ADP-ribose can mediate calcium homeostasis by affecting
TRPM2 receptors and ryanodine receptors; and sirtuins and PARPs appear
to play key roles in aging, cell death and a variety of cellular
functions. It has also been indicated that NADH and NAD+ can be
transported across plasma membranes of cells, and that extracellular
NAD+ may be a new signaling molecule. Our latest studies have shown
that intranasal NAD+ administration can profoundly decrease ischemic
brain damage. These new pieces of information have fundamentally
changed our understanding about NAD+ and NADH, suggesting novel
paradigms about the metabolism and biological activities of NAD+ and
NADH. Based on this information, it is tempted to hypothesize that NAD
+ and NADH, together with ATP and Ca2+, may be four most fundamental
components in life, which can significantly affect nearly all major
biological processes. Future studies on NAD+ and NADH may not only
elucidate some fundamental mysteries in biology, but also provide
novel insights for interfering aging and many disease processes.


PMID: 16720381 [PubMed - indexed for MEDLINE]