Volume 101, 1 February 2016, Pages 13–26
Abstract
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.
Graphical abstract
Chemical compounds cited in this article
- Nicotinamide (PubChem CID 936);
- Nicotinic acid (PubChem CID 938);
- Nicotinamide mononucleotide (PubChem CID 14180);
- Nicotinamide ribose (PubChem CID 439924);
- EX527 (PubChem CID 5113032);
- Cambinol (PubChem CID3246390);
- FK866 (PubChem CID 6914657);
- GMX1777 (PubChem CID 9961434);
- CHS828 (PubChem CID 148198);
- GNE-617 (PubChem CID 68277611)
Abbreviations
- ADP, adenosine-5′-phosphate;
- ADPR, ADP ribose;
- cADPR, cyclic ADPR;
- AIF, apoptosis-inducing factor;
- AMP, adenosine-5′-phosphate;
- AMPK, AMP-activated protein kinase;
- ANT, adenine nucleotide translocator;
- ART2, ADP-ribosyltransferase 2;
- ATG, autophagy related genes;
- ATP, adenosine-5′-triphosphate;
- ARH, ADP-ribosylhydrolase;
- BCL-XL, B-cell lymphoma-extra large;
- BIRC3, baculoviral IAP repeat-containing protein 3;
- BRCA1/2, breast cancer 1/2;
- CAD, caspase activated DNAse;
- cIAP2, cellular inhibitor of apoptosis protein;
- FOXO3, forkhead box O3;
- DNA, deoxyribonucleic acid;
- ESR1, estrogen receptor 1;
- GPR109A, G protein-coupled receptor;
- H2AFX, H2A histone family member X;
- HCAR2, hydroxycarboxylic acid receptor 2;
- HER, human epidermal growth factor receptor 2;
- HK1/2, hexokinase 1/2;
- IDO, indoleamine 2,3-dioxygenase;
- IL-1β, interleukin-1β;
- LDHA, lactate dehydrogenase A;
- LPS, lipopolysaccharide;
- MAP1LC3A, microtubule-associated proteins 1A/1B light chain 3A, MDM2, mouse double minute 2 homolog;
- MEF, mouse embryonic fibroblast;
- MLKL, mixed lineage kinase domain-like;
- MMS, methylmethane sulfonate;
- MNNG, methyl-N′-nitro-N-nitrosoguanidine;
- NA, nicotinic acid;
- NAADP, nicotinic acid adenine dinucleotide phosphate;
- NAD, nicotinamide adenine dinucleotide;
- Nam, nicotinamide;
- NAMPT, nicotinamide phosphoribosyl tranferase;
- NAPRT(1), nicotinate phosphoribosyltransferase;
- NAR, NA riboside;
- NF-κB, nuclear factor kappa B;
- NICD, NAD+-induced cell death;
- NMDA, N-methyl-d-aspartate;
- NMN, nicotinamide mononucleotide;
- NMNAT, Nam mononucleotide adenylyltransferase;
- NR, Nam riboside;
- NUDT5/9, nudix (nucleoside diphosphate linked moiety X)-type motif 5/9;
- PML, promyelocytic leukemia protein;
- PPIF, peptidyl-prolyl cis–trans isomerase F;
- OGG1, 8-oxoguanidine-DNA glycosylase 1;
- P2(R)X7, purinergic (receptor) P2X, ligand gated ion channel 7;
- PAR, poly ADP-ribose;
- MPT, mitochondrial permeability transition;
- PARG, PAR glycohydrolase;
- PARP, PAR polymerase;
- RELA, v-rel avian reticuloendotheliosis viral oncogene homolog A;
- RIPK1/3, receptor interacting serine-threonine kinase 1/3;
- RNA, ribonucleic acid;
- ROS, reactive oxygen species;
- shRNA, short hairpin RNA;
- siRNA, small interfering RNA;
- SARM1, sterile alpha and TIR motif containing 1 TLR, toll-like receptors;
- TNF, tumor necrosis factor;
- TNFR1, TNF receptor 1;
- TNFSF, TNF (ligand) superfamily member;
- TNFRSF, TNFR superfamily member;
- TRAIL, TNF-related apoptosis-inducing ligand;
- tRNA, transfer RNA;
- TRPM2, transient receptor potential cation channel, subfamily M, member 2;
- TRPT, tRNA 2′-phosphotransferase 1
Keywords
- Regulated cell death;
- Apoptosis;
- Parthanatos;
- Necroptosis;
- NAMPT;
- NAD
Copyright © 2015 Elsevier Inc. All rights reserved.
