Keeping the balance in NAD metabolism

Area of Science:

• Biochemistry and molecular biology
• Cellular signaling and metabolism

Background:

• Nicotinamide adenine dinucleotide (NAD) has evolved from a redox carrier to a key signaling molecule.
• NAD regulates fundamental cellular processes like DNA repair, cell cycle, gene expression, and calcium signaling.
• Non-redox functions necessitate continuous NAD biosynthesis, primarily through nicotinamide salvage, with other precursors also supporting NAD levels.

Purpose of the Study:

• To review recent advancements in understanding NAD metabolism and its regulatory roles.
• To discuss the challenges and future directions in NAD research.
• To highlight the therapeutic potential of NAD restoration in disease models.

Main Methods:

• Literature review of NAD research.
• Analysis of NAD biosynthesis and consumption pathways.
• Examination of NAD's role in cellular signaling and disease.

Main Results:

• NAD is a substrate for regulatory proteins like sirtuins and ADP-ribosyltransferases.
• NAD-dependent signaling involves cleavage of NAD into ADP-ribosyl and nicotinamide.
• Subcellular compartmentalization of NAD pools is recognized, with limited understanding of their generation and function.
• Impaired NAD biosynthesis or increased consumption is linked to aging and pathologies.
• Neuronal insults cause axonal NAD depletion, leading to degeneration, with NAD precursors offering partial rescue.
• Restoring NAD levels demonstrates therapeutic benefits in various disease models.

Conclusions:

• NAD plays critical roles in cellular regulation beyond redox reactions.
• Maintaining cellular NAD homeostasis is vital for health and preventing age-related diseases.
• NAD precursor supplementation and biosynthesis stimulation offer promising therapeutic strategies for diverse pathologies.