Nicotinamide adenine dinucleotide has several essential roles in metabolism. It acts as acoenzyme inredox reactions, as a donor of ADP-ribose moieties in ADP-ribosylation reactions, as a precursor of thesecond messenger molecule cyclic ADP-ribose, as well as acting as a substrate for bacterial DNA ligases and a group of enzymes called sirtuins that use NAD+ to remove acetyl groups from proteins. In addition to these metabolic functions, NAD+ emerges as an adenine nucleotide that can be released from cells spontaneously and by regulated mechanisms, and can therefore have important extracellularroles.
 
The enzymes that make and use NAD+ and NADH are important in both pharmacology and the research into future treatments for disease. Drug design and drug development exploits NAD+ in three ways: as a direct target of drugs, by designing enzyme inhibitors or activators based on its structure that change the activity of NAD-dependent enzymes, and by trying to inhibit NAD+biosynthesis.
 
The coenzyme NAD+ is not itself currently used as a treatment for any disease. However, it is being studied for its potential use in the therapy of neurodegenerative diseases such asAlzheimer's andParkinson disease. Evidence on the benefit of NAD+ in neurodegeneration is mixed; some studies inmice have produced promising results whereas a placebo-controlled clinical trial in humans failed to show any effect.
 
NAD+ is also a direct target of the drug isoniazid, which is used in the treatment oftuberculosis, an infection caused by Mycobacterium tuberculosis. Isoniazid is a prodrug and once it has entered the bacteria, it is activated by a peroxidase enzyme, which oxidizes the compound into a free radicalform. This radical then reacts with NADH, to produce adducts that are very potent inhibitors of the enzymes enoyl-acyl carrier protein reductase, and dihydrofolate reductase. In one experiment, mice given NAD for one week had improved nuclear-mitochrondrial communication.