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BRIEF RESEARCH REPORT article

Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1519066
This article is part of the Research Topic Opportunities and Challenges in Drug Repurposing View all 3 articles

The clinically applied PARP inhibitor talazoparib ameliorates imiquimod-induced psoriasis in mice without reducing skin inflammation

Provisionally accepted
Petra Molnár Petra Molnár 1,2Máté Ágoston Demény Máté Ágoston Demény 3Beáta Várkonyi Beáta Várkonyi 3Zsuzsanna Polgár Zsuzsanna Polgár 3Ágnes Pór Ágnes Pór 4Ilona Kovács Ilona Kovács 4Andrea Szegedi Andrea Szegedi 5Attila Gábor Szöllősi Attila Gábor Szöllősi 2Magdolna Szántó Magdolna Szántó 1,3*
  • 1 University of Debrecen, Debrecen, Hungary
  • 2 Department of Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
  • 3 Department of Medical Chemistry, Faculty of Medicinie, University of Debrecen, Debrecen, Hungary
  • 4 Department of Pathology, Kenézy Gyula Hospital, University of Debrecen, Debrecen, Hungary
  • 5 Department of Dermatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

The final, formatted version of the article will be published soon.

    Background: Considering the role PARPs play in inflammation, we assessed the effect of PARP inhibition in an inflammatory skin condition, psoriasis, to explore novel avenues for the potential repurposing of PARP inhibitors that are currently used in tumour therapy.The imiquimod (IMQ)-induced model of psoriasis was applied in BALB/c mice.Mice received daily intraperitoneal injection of either one of four PARP inhibitors or their vehicle prior to treatment of the shaved back skin of mice with IMQ-containing cream or control cream for four days. The appearance of the skin of mice was scored daily according to the extent of erythema, induration and scaling. The most effective PARP inhibitor was selected for detailed studies on mouse skin and in a human keratinocyte cell line.Results: Of the PARP inhibitors, talazoparib and rucaparib improved the imiquimod-induced symptoms on mouse skin. Application of talazoparib in the psoriasis model resulted in maintained terminal differentiation and reduced proliferation of epidermal keratinocytes.Conversely, talazoparib also enhanced the production of pro-inflammatory chemokines in the skin of mice. These effects of talazoparib was associated with increased mitochondrial production of reactive oxygen species and a consequent activation of pro-apoptotic and proinflammatory pathways in keratinocytes.keratinocytes that may be beneficial in psoriasis. Despite the fact that talazoparib exerted a proinflammatory effect in the skin, which is not unprecedented in anti-psoriatic therapy, these findings may advance the conduction of pre-clinical and clinical trials with PARP inhibitors in psoriasis management.

    Keywords: PARP inhibitor, Psoriasis, Terminal differentiation, Apoptosis, Mitochondria, drug repurposing

    Received: 29 Oct 2024; Accepted: 27 Jan 2025.

    Copyright: © 2025 Molnár, Demény, Várkonyi, Polgár, Pór, Kovács, Szegedi, Szöllősi and Szántó. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Magdolna Szántó, University of Debrecen, Debrecen, Hungary

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