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Updated: Dec 31, 2025

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PARP-1 deregulation in multiple sclerosis.

Maria Meira1, Claudia Sievers1, Francine Hoffmann1

  • 1Departments of Biomedicine and Neurology, University Hospital Basel, Switzerland.

Multiple Sclerosis Journal - Experimental, Translational and Clinical
|January 4, 2020
PubMed
Summary

Poly (ADP-ribose) polymerase 1 (PARP-1) is upregulated in multiple sclerosis lymphocytes, suggesting a role in disease pathogenesis. Its elevated expression in progressive multifocal leukoencephalopathy indicates potential therapeutic targets for these conditions.

Keywords:
JCVPARP-1multiple sclerosisnatalizumabprogressive multifocal leukoencephalopathy (PML)

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Area of Science:

  • Immunology
  • Neuroimmunology
  • Molecular Biology

Background:

  • Poly (ADP-ribose) polymerase 1 (PARP-1) is crucial in immune and inflammatory responses.
  • PARP-1 is a potential therapeutic target for immunomodulation in multiple sclerosis (MS) and natalizumab-associated progressive multifocal leukoencephalopathy (PML).

Purpose of the Study:

  • To investigate the expression of PARP-1 and its downstream effectors in MS patients.
  • To analyze PARP-1 expression during natalizumab treatment in MS patients.

Main Methods:

  • Real-time reverse transcriptase polymerase chain reaction was used to study transcriptional expression.
  • Analysis was performed on CD4+ T cells, CD8+ T cells, CD14+ cells, B cells, and peripheral blood mononuclear cells.
  • Samples were obtained from healthy volunteers and MS patients (untreated, natalizumab-treated, non-PML, and PML).

Main Results:

  • PARP-1 expression was higher in CD4+ T, CD8+ T, and B cells of untreated MS patients compared to healthy controls.
  • Natalizumab treatment normalized PARP-1 expression in T cells but not B cells.
  • Increased PARP-1 in B cells correlated with decreased TGFBR1/TGFBR2/BCL6 expression; higher PARP-1 was observed in PML cases.

Conclusions:

  • Upregulated PARP-1 in MS lymphocytes suggests a role in immune pathogenesis.
  • Elevated PARP-1 in PML cases indicates involvement in disease mechanisms.
  • PARP-1 inhibitors represent a promising therapeutic strategy for MS and natalizumab-associated PML.