Therapeutic Potentials of Poly (ADP‐Ribose) Polymerase 1 (PARP1) Inhibition in Multiple Sclerosis and Animal Models: Concept Revisiting
Abstract Poly (ADP‐ribose) polymerase 1 (PARP1) plays a fundamental role in DNA repair and gene expression. Excessive PARP1 hyperactivation, however, has been associated with cell death. PARP1 and/or its activity are dysregulated in the immune and central nervous system of multiple sclerosis (MS) pa...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-02-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202102853 |
| _version_ | 1819278407663353856 |
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| author | Yan Wang David Pleasure Wenbin Deng Fuzheng Guo |
| author_facet | Yan Wang David Pleasure Wenbin Deng Fuzheng Guo |
| author_sort | Yan Wang |
| collection | DOAJ |
| description | Abstract Poly (ADP‐ribose) polymerase 1 (PARP1) plays a fundamental role in DNA repair and gene expression. Excessive PARP1 hyperactivation, however, has been associated with cell death. PARP1 and/or its activity are dysregulated in the immune and central nervous system of multiple sclerosis (MS) patients and animal models. Pharmacological PARP1 inhibition is shown to be protective against immune activation and disease severity in MS animal models while genetic PARP1 deficiency studies reported discrepant results. The inconsistency suggests that the function of PARP1 and PARP1‐mediated PARylation may be complex and context‐dependent. The article reviews PARP1 functions, discusses experimental findings and possible interpretations of PARP1 in inflammation, neuronal/axonal degeneration, and oligodendrogliopathy, three major pathological components cooperatively determining MS disease course and neurological progression, and points out future research directions. Cell type specific PARP1 manipulations are necessary for revisiting the role of PARP1 in the three pathological components prior to moving PARP1 inhibition into clinical trials for MS therapy. |
| first_indexed | 2024-12-24T00:11:31Z |
| format | Article |
| id | doaj.art-6c76caf8d7394ec384e23e020dec9400 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-12-24T00:11:31Z |
| publishDate | 2022-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-6c76caf8d7394ec384e23e020dec94002022-12-21T17:24:52ZengWileyAdvanced Science2198-38442022-02-0195n/an/a10.1002/advs.202102853Therapeutic Potentials of Poly (ADP‐Ribose) Polymerase 1 (PARP1) Inhibition in Multiple Sclerosis and Animal Models: Concept RevisitingYan Wang0David Pleasure1Wenbin Deng2Fuzheng Guo3Department of Neurology School of Medicine University of California Davis CA 95817 USADepartment of Neurology School of Medicine University of California Davis CA 95817 USASchool of Pharmaceutical Sciences (Shenzhen) Sun Yat‐sen University Guangzhou 510006 ChinaDepartment of Neurology School of Medicine University of California Davis CA 95817 USAAbstract Poly (ADP‐ribose) polymerase 1 (PARP1) plays a fundamental role in DNA repair and gene expression. Excessive PARP1 hyperactivation, however, has been associated with cell death. PARP1 and/or its activity are dysregulated in the immune and central nervous system of multiple sclerosis (MS) patients and animal models. Pharmacological PARP1 inhibition is shown to be protective against immune activation and disease severity in MS animal models while genetic PARP1 deficiency studies reported discrepant results. The inconsistency suggests that the function of PARP1 and PARP1‐mediated PARylation may be complex and context‐dependent. The article reviews PARP1 functions, discusses experimental findings and possible interpretations of PARP1 in inflammation, neuronal/axonal degeneration, and oligodendrogliopathy, three major pathological components cooperatively determining MS disease course and neurological progression, and points out future research directions. Cell type specific PARP1 manipulations are necessary for revisiting the role of PARP1 in the three pathological components prior to moving PARP1 inhibition into clinical trials for MS therapy.https://doi.org/10.1002/advs.202102853demyelinationinflammatory demyelinating diseasemultiple sclerosisneuroinflammationneuronal/axonal degenerationPARP1 |
| spellingShingle | Yan Wang David Pleasure Wenbin Deng Fuzheng Guo Therapeutic Potentials of Poly (ADP‐Ribose) Polymerase 1 (PARP1) Inhibition in Multiple Sclerosis and Animal Models: Concept Revisiting Advanced Science demyelination inflammatory demyelinating disease multiple sclerosis neuroinflammation neuronal/axonal degeneration PARP1 |
| title | Therapeutic Potentials of Poly (ADP‐Ribose) Polymerase 1 (PARP1) Inhibition in Multiple Sclerosis and Animal Models: Concept Revisiting |
| title_full | Therapeutic Potentials of Poly (ADP‐Ribose) Polymerase 1 (PARP1) Inhibition in Multiple Sclerosis and Animal Models: Concept Revisiting |
| title_fullStr | Therapeutic Potentials of Poly (ADP‐Ribose) Polymerase 1 (PARP1) Inhibition in Multiple Sclerosis and Animal Models: Concept Revisiting |
| title_full_unstemmed | Therapeutic Potentials of Poly (ADP‐Ribose) Polymerase 1 (PARP1) Inhibition in Multiple Sclerosis and Animal Models: Concept Revisiting |
| title_short | Therapeutic Potentials of Poly (ADP‐Ribose) Polymerase 1 (PARP1) Inhibition in Multiple Sclerosis and Animal Models: Concept Revisiting |
| title_sort | therapeutic potentials of poly adp ribose polymerase 1 parp1 inhibition in multiple sclerosis and animal models concept revisiting |
| topic | demyelination inflammatory demyelinating disease multiple sclerosis neuroinflammation neuronal/axonal degeneration PARP1 |
| url | https://doi.org/10.1002/advs.202102853 |
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