Sirtuin and Poly(ADP-ribose) polymerase (SIRT and PARP) (SIRT and PARP)

Sirtuins (SIRTs) and Poly(ADP-ribose) polymerases (PARPs) are two major families of enzymes that utilize nicotinamide adenine dinucleotide (NAD+) as a co-substrate, creating a competitive relationship for the cellular NAD+ pool (Cantó et al., 2015, Cell Metabolism). Sirtuins are a class of NAD+-dependent deacetylases (SIRT1-7) involved in regulating metabolic homeostasis, DNA repair, and longevity by modifying histones and transcription factors (Imai & Guarente, 2014, Trends in Cell Biology). PARPs, particularly PARP1, are essential for detecting and signaling DNA damage, facilitating repair through the synthesis of poly(ADP-ribose) chains (Gupte et al., 2017, Genes & Development). In disease contexts, PARP overactivation can deplete NAD+ levels, impairing sirtuin activity and contributing to metabolic dysfunction and aging-related pathologies (Mouchiroud et al., 2013, Cell). Conversely, PARP inhibitors are clinically established for treating BRCA-mutated cancers by inducing synthetic lethality, while sirtuin activators are being explored for their potential to treat metabolic and neurodegenerative diseases (Lord & Ashworth, 2017, Science). The interplay between these two enzyme families is a critical focal point for therapeutic strategies aimed at balancing cellular energy and genomic stability.

Other names

Sirtuins and PARPsNAD+-consuming enzymesSIRT/PARP axisSirtuin familyPARP family

PARP inhibitors induce synthetic lethality by trapping PARP on DNA and preventing repair of single-strand breaks in homologous recombination-deficient cells (Lord & Ashworth, 2017, Science). Sirtuin activators enhance the deacetylation of target proteins like PGC-1alpha and p53 to regulate metabolic efficiency and cellular stress responses (Imai & Guarente, 2014, Trends in Cell Biology).