Complex role of nicotinamide adenine dinucleotide in the regulation of programmed cell death pathways.
Over the past few years, a growing body of experimental observations has led to the identification of novel and alternative programs of regulated cell death. Recently, autophagic cell death and controlled forms of necrosis have emerged as major alternatives to apoptosis, the best characterized form of regulated cell demise. These recently identified, caspase-independent, forms of cell death appear to play a role in the response to several forms of stress, and their importance in different pathological conditions such as ischemia, infection and inflammation has been recognized. The functional link between cell metabolism and survival has also been the matter of recent studies. Nicotinamide adenine dinucleotide (NAD(+)) has gained particular interest due to its role in cell energetics, and as a substrate for several families of enzymes, comprising poly ADP-ribose polymerases (PARPs) and sirtuins, involved in numerous biological functions including cell survival and death. The recently uncovered diversity of cell death programs has led us to reevaluate the role of this important metabolite as a universal pro-survival factor, and to discuss the potential benefits and limitations of pharmacological approaches targeting NAD(+) metabolism.
Laboratory of Immunobiology, Department of Molecular Biology, Université Libre de Bruxelles, Gosselies, Belgium.
Nicolas
N
Preyat
Laboratory of Immunobiology, Department of Molecular Biology, Université Libre de Bruxelles, Gosselies, Belgium. Electronic address: oleo@ulb.ac.be.
Oberdan
O
Leo
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D055808:Drug Discovery; D015507:Drugs, Investigational / Q000494:pharmacology; D006801:Humans; D008954:Models, Biological; D009243:NAD / Q000502:physiology*; D009336:Necrosis / Q000201:enzymology / Q000378:metabolism* / Q000517:prevention & control
D015507:Drugs, Investigational; D009243:NAD
Apoptosis; CHS828 (PubChem CID 148198); Cambinol (PubChem CID3246390); EX527 (PubChem CID 5113032); FK866 (PubChem CID 6914657); GMX1777 (PubChem CID 9961434); GNE-617 (PubChem CID 68277611); NAD; NAMPT; Necroptosis; Nicotinamide (PubChem CID 936); Nicotinamide mononucleotide (PubChem CID 14180); Nicotinamide ribose (PubChem CID 439924); Nicotinic acid (PubChem CID 938); Parthanatos; Regulated cell death