The Role of PARPs in Inflammation—And Metabolic—Related Diseases: Molecular Mechanisms and Beyond

Abstract

Poly(ADP-ribosyl)ation (PARylation) is an essential post-translational modification catalyzed by poly(ADP-ribose) polymerase (PARP) enzymes. Poly(ADP-ribose) polymerase 1 (PARP1) is a well-characterized member of the PARP family. PARP1 plays a crucial role in multiple biological processes and PARP1 activation contributes to the development of various inflammatory and malignant disorders, including lung inflammatory disorders, cardiovascular disease, ovarian cancer, breast cancer, and diabetes. In this review, we will focus on the role and molecular mechanisms of PARPs enzymes in inflammation- and metabolic-related diseases. Specifically, we discuss the molecular mechanisms and signaling pathways that PARP1 is associated with in the regulation of pathogenesis. Recently, increasing evidence suggests that PARP inhibition is a promising strategy for intervention of some diseases. Thus, our in-depth understanding of the mechanism of how PARPs are activated and how their signaling downstream effecters can provide more potential therapeutic targets for the treatment of the related diseases in the future is crucial.

Repositioning PARP inhibitors for SARS‐CoV‐2 infection(COVID‐19); a new multi‐pronged therapy for acute respiratory distress syndrome?

“…Subsequently, it has also been shown that the product of the PARP reaction, that is, PAR, can also trigger apoptosis‐inducing factor (AIF) release that promotes a specific programmed cell death pathway called “parthanatos” (Fatokun, Dawson, & Dawson, 2014). Relevant to inflammatory normal tissue damage in general and acute respiratory distress syndrome (ARDS) in particular is the role of oxidative and nitrosative stress, which is integral to inflammation and causes DNA strand breakage that massively activates PARP (Bai & Virag, 2012; Ke et al, 2019). Indeed, PARP can actively increase and prolong inflammation through a vicious cycle of ROS/RNS‐induced DNA damage, PARP‐mediated necrosis and increase in inflammatory cytokines (Figure 1).…”

A novel predicted ADP-ribosyltransferase family conserved in eukaryotic evolution

“…It may direct intracellular signaling to parthanatos (type of programmed death) [96][97][98], whereas such scenario implies induction of inflammatory response to infection. Poly-ADP-ribosylation is known to influence the stability of transcripts encoding proinflammatory cytokines [99]. For an uncharacterised protein, its physical interactors may shed light on its function.…”

Transgelin interacts with PARP1 and affects Rho signaling pathway in human colon cancer cells

“…Poly ADPribose polymerase-1 is encoded by PARP1 and the molecular weight is 113kDa. It is involved in DNA repair, cell cycle, cell death, tumorigenesis and other cellular processes [33][34][35][36]. Its N-terminal has the DNA binding domain consisting of two zinc finger motifs and a nuclear localization sequence [37].…”