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Roles of NAD(+) / NADH and NADP(+) / NADPH in cell death

Weiliang Xia1, Zheng Wang, Qing Wang

  • 1Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.

Current Pharmaceutical Design
|January 20, 2009
PubMed

Insights

Nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) are emerging as key regulators of cell death. Their roles in oxidative stress and cellular functions suggest new therapeutic targets for various diseases.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Medicine

Background:

  • Emerging evidence highlights the critical roles of NAD (NAD+, NADH) and NADP (NADP+, NADPH) in cellular life and death processes.
  • NAD-dependent enzymes, including poly (ADP-ribose) polymerases and sirtuins, are implicated in cell death pathways.
  • NAD and NADP influence cell survival through diverse mechanisms, including mitochondrial function, oxidative stress, and calcium homeostasis.

Purpose of the Study:

  • To review and synthesize the current understanding of NAD and NADP roles in cell death.
  • To explore the involvement of these coenzymes in various cellular functions relevant to survival and death.
  • To identify potential therapeutic strategies targeting NAD and NADP pathways for disease treatment.

Main Methods:

  • Literature review and synthesis of existing research on NAD, NADP, and cell death.
  • Analysis of studies investigating NAD-dependent enzymes (PARPs, sirtuins) in cell death.
  • Examination of the role of NADP in oxidative stress and cellular antioxidation systems.

Main Results:

  • NAD influences cell death via mitochondrial permeability transition, apoptosis-inducing factor, and GAPDH.
  • NAD affects cell survival through modulation of calcium homeostasis, gene expression, and immune functions.
  • NADPH plays a significant role in mediating cell death through oxidative stress, acting as an antioxidant and a generator of reactive oxygen species via NADPH oxidase.

Conclusions:

  • NAD and NADP are fundamental factors in regulating cell death.
  • Understanding the novel biological properties of NAD and NADP can elucidate cell death mechanisms.
  • Targeting NAD and NADP pathways offers promising therapeutic avenues for various diseases.

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