PARPs and PAR as novel pharmacological targets for the treatment of stress granule-associated disorders.

PARPs and PAR as novel pharmacological targets for the treatment of stress granule-associated disorders. Biochem Pharmacol. 2019 May 15;: Authors: Grimaldi G, Catara G, Palazzo L, Corteggio A, Valente C, Corda D Abstract Among the post-translational modifications, ADP-ribosylation has been for long time the least integrated in the scheme of the structural protein modifications affecting physiological functions. In spite of the original findings on bacterial-dependent ADP-ribosylation catalysed by toxins such as cholera and pertussis toxin, only with the discovery of the poly-ADP-ribosyl polymerase (PARP) family the field has finally expanded and the role of ADP-ribosylation has been recognised in both physiological and pathological processes, including cancer, infectious and neurodegenerative diseases. This is now a rapidly expanding field of investigation, centred on the role of the different PARPs and their substrates in various diseases, and on the potential of PARP inhibitors as novel pharmacological tools to be employed in relevant pathological context. In this review we analyse the role that members of the PARP family and poly-ADP-ribose (PAR; the product of PARP1 and PARP5a activity) play in the processes following the exposure of cells to different stresses. The cell response that arises following conditions such as heat, osmotic, oxidative stresses or viral infection relies on the formation of stress granules, which are tran...
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research