PARP-1 deregulation in multiple sclerosis.
- Meira M Departments of Biomedicine and Neurology, University Hospital Basel, Switzerland.
- Sievers C Departments of Biomedicine and Neurology, University Hospital Basel, Switzerland.
- Hoffmann F Departments of Biomedicine and Neurology, University Hospital Basel, Switzerland.
- Bodmer H Departments of Biomedicine and Neurology, University Hospital Basel, Switzerland.
- Derfuss T Departments of Biomedicine and Neurology, University Hospital Basel, Switzerland.
- Kuhle J Departments of Biomedicine and Neurology, University Hospital Basel, Switzerland.
- Haghikia A Department of Neurology, Ruhr-University Bochum, Germany.
- Kappos L Departments of Biomedicine and Neurology, University Hospital Basel, Switzerland.
- Lindberg RL Departments of Biomedicine and Neurology, University Hospital Basel, Switzerland.
- 2020-01-04
Published in:
- Multiple sclerosis journal - experimental, translational and clinical. - 2019
English
Background
Poly (ADP-ribose) polymerase 1 (PARP-1) plays pivotal roles in immune and inflammatory responses. Accumulating evidence suggests PARP-1 as a promising target for immunomodulation in multiple sclerosis and natalizumab-associated progressive multifocal leukoencephalopathy.
Objective
This study explores expression of PARP-1 and downstream effectors in multiple sclerosis and during natalizumab treatment.
Methods
Transcriptional expressions were studied by real-time reverse transcriptase polymerase chain reaction on CD4+T/CD8+T/CD14+/B cells and peripheral blood mononuclear cells from healthy volunteers, untreated and natalizumab-treated non-progressive multifocal leukoencephalopathy and progressive multifocal leukoencephalopathy multiple sclerosis patients.
Results
PARP-1 expression was higher in CD4+T, CD8+T and B cells from untreated patients compared to healthy volunteers. Natalizumab treatment restored deregulated PARP-1 expression in T cells but not in B cells. Sustained upregulation of PARP-1 was associated with decreased expression of downstream PARP-1 factors such as TGFBR1/TGFBR2/BCL6 in B cells. Notably, a higher expression of PARP-1 was detected in progressive multifocal leukoencephalopathy patients.
Conclusions
Given the importance of PARP-1 in inflammatory processes, its upregulation in multiple sclerosis lymphocyte populations suggests a potential role in the immune pathogenesis of multiple sclerosis. Strikingly higher PARP-1 expression in progressive multifocal leukoencephalopathy cases suggests its involvement in progressive multifocal leukoencephalopathy disease pathomechanisms. These results further support the value of PARP-1 inhibitors as a potential novel therapeutic strategy for multiple sclerosis and natalizumab-associated progressive multifocal leukoencephalopathy.
Poly (ADP-ribose) polymerase 1 (PARP-1) plays pivotal roles in immune and inflammatory responses. Accumulating evidence suggests PARP-1 as a promising target for immunomodulation in multiple sclerosis and natalizumab-associated progressive multifocal leukoencephalopathy.
Objective
This study explores expression of PARP-1 and downstream effectors in multiple sclerosis and during natalizumab treatment.
Methods
Transcriptional expressions were studied by real-time reverse transcriptase polymerase chain reaction on CD4+T/CD8+T/CD14+/B cells and peripheral blood mononuclear cells from healthy volunteers, untreated and natalizumab-treated non-progressive multifocal leukoencephalopathy and progressive multifocal leukoencephalopathy multiple sclerosis patients.
Results
PARP-1 expression was higher in CD4+T, CD8+T and B cells from untreated patients compared to healthy volunteers. Natalizumab treatment restored deregulated PARP-1 expression in T cells but not in B cells. Sustained upregulation of PARP-1 was associated with decreased expression of downstream PARP-1 factors such as TGFBR1/TGFBR2/BCL6 in B cells. Notably, a higher expression of PARP-1 was detected in progressive multifocal leukoencephalopathy patients.
Conclusions
Given the importance of PARP-1 in inflammatory processes, its upregulation in multiple sclerosis lymphocyte populations suggests a potential role in the immune pathogenesis of multiple sclerosis. Strikingly higher PARP-1 expression in progressive multifocal leukoencephalopathy cases suggests its involvement in progressive multifocal leukoencephalopathy disease pathomechanisms. These results further support the value of PARP-1 inhibitors as a potential novel therapeutic strategy for multiple sclerosis and natalizumab-associated progressive multifocal leukoencephalopathy.
- Language
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- English
- Open access status
- gold
- Identifiers
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- DOI 10.1177/2055217319894604
- PMID 31897308
- Persistent URL
- https://sonar.ch/global/documents/5858
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