NAD and NADH in brain functions, brain diseases and brain aging

NAD and NADH in brain functions, brain diseases and brain aging

1. ABSTRACT
Numerous studies have suggested that NAD+ and
NADH mediate multiple major biological processes,
including calcium homeostasis, energy metabolism,
mitochondrial functions, cell death and aging. In
particular, NAD+ and NADH have emerged as novel,
fundamental regulators of calcium homeostasis. It appears
that most of the components in the metabolic pathways of
NAD+ and NADH, including poly(ADP-ribose), ADPribose,
cyclic ADP-ribose, O-acetyl-ADP-ribose,
nicotinamide and kynurenine, can produce significant
biological effects. This exquisiteness of NAD+ and
NADH metabolism could epitomize the exquisiteness of
life, through which we may grasp the intrinsic harmony
life has evolved to produce. The exquisiteness also
suggests a central regulatory role of NAD+ and NADH
in life. It is tempted to propose that NAD+ and NADH,
together with ATP and Ca2+, constitute a Central
Regulatory Network of life. Increasing evidence has
also suggested that NAD+ and NADH play important
roles in multiple biological processes in brains, such as
neurotransmission and learning and memory. NAD+ and
NADH may also mediate brain aging and the tissue
damage in various brain illnesses. Our latest studies
have suggested that NADH can be transported across the
plasma membranes of astrocytes, and that NAD+
administration can markedly decrease ischemic brain
injury. Based on this information, it is proposed that
NAD+ and NADH are fundamental mediators of brain
functions, brain senescence and multiple brain diseases.
Because numerous properties of NAD+ and NADH
remain unclear, future studies regarding NAD+ and
NADH may expose some fundamental mechanisms
underlying brain functions, brain pathologies and brain
aging.

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