NAD and NADH in cellular functions and cell death

NAD and NADH in cellular functions and cell death

1. ABSTRACT
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…

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