title: Targeting poly(ADP-ribose) polymerase-1 as a promising approach for immunomodulation in multiple sclerosis?
abstract: Despite significant advancement in developing therapies for multiple sclerosis (MS), drugs that cure this devastating disorder are an unmet need. Among the remedies showing efficacy in preclinical MS models, inhibitors of poly(ADP-ribose) polymerase (PARP)-1 have gained great momentum. Emerging evidence demonstrates that PARP-1 inhibitors epigenetically regulate gene expression and finely tune transcriptional activation in immune and neural cells. In this review, we present an appraisal of the effects of PARP-1 and its inhibitors on immune activation, with particular emphasis on the processes taking place during the autoimmune attack directed against the central nervous system. One explanation is that drugs inhibiting PARP-1 activity protect from neuroinflammation in MS models via immunomodulation and direct neuroprotection. PARP-1 inhibitors have already reached the clinical arena as cancer treatments, and observations made in treating these patients could help advance treatments for MS.
authors.affiliation: Department of Preclinical and Clinical Pharmacology, Viale Pieraccini 6, University of Florence, 50139 Florence, Italy. leonardo.cavone@unifi.it
authors.forename: Leonardo
authors.initials: L
authors.lastname: Cavone
authors.forename: Alberto
authors.initials: A
authors.lastname: Chiarugi
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000276:immunology*; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases