Poly(ADP-Ribose) polymerases new players in the pathogenesis of exocrine pancreatic diseases

Neus Martínez-Bosch, Martin E Fernandez-Zapico, Pilar Navarro, José Yélamos

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The poly(ADP-ribose) polymerase (PARP) enzymes were initially characterized as sensors of DNA breaks but are now known to play key roles not only in the DNA damage response but also in regulating numerous molecular processes, such as gene transcription. Furthermore, these polymerases have emerged as key players in the pathogenesis of multiple diseases, providing promising therapeutic targets for pathologies such as cardiovascular disorders, neurodegenerative diseases, and cancer. In recent years, PARPs have been implicated in the pathogenesis of pancreatitis and pancreatic cancer, and PARP inhibition has been proposed as a valuable strategy for treating these two important gastrointestinal tract disorders. For instance, in preclinical mouse models, pancreatitis was significantly attenuated after genetic or pharmacological PARP inactivation, and several clinical trials have demonstrated promising responses to PARP inhibitors in pancreatic cancer patients. In this review, we summarize the current understanding of PARP functions in these two dismal pathologies and discuss the next steps necessary to determine whether PARP inhibitors will finally make the difference in treating pancreatitis and pancreatic cancer successfully.

Original languageEnglish (US)
Pages (from-to)234-241
Number of pages8
JournalAmerican Journal of Pathology
Volume186
Issue number2
DOIs
StatePublished - Feb 1 2016

Fingerprint

Pancreatic Diseases
Poly(ADP-ribose) Polymerases
Pancreatic Neoplasms
Pancreatitis
Pathology
DNA Breaks
Neurodegenerative Diseases
DNA Damage
Gastrointestinal Tract
Clinical Trials
Pharmacology
Enzymes
Genes
Neoplasms
Poly(ADP-ribose) Polymerase Inhibitors
Therapeutics

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Poly(ADP-Ribose) polymerases new players in the pathogenesis of exocrine pancreatic diseases. / Martínez-Bosch, Neus; Fernandez-Zapico, Martin E; Navarro, Pilar; Yélamos, José.

In: American Journal of Pathology, Vol. 186, No. 2, 01.02.2016, p. 234-241.

Research output: Contribution to journalArticle

Martínez-Bosch, Neus ; Fernandez-Zapico, Martin E ; Navarro, Pilar ; Yélamos, José. / Poly(ADP-Ribose) polymerases new players in the pathogenesis of exocrine pancreatic diseases. In: American Journal of Pathology. 2016 ; Vol. 186, No. 2. pp. 234-241.
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