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Existing Evidence for the Repurposing of PARP-1 Inhibitors in Rare Demyelinating Diseases

SIMPLE SUMMARY: Poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors are successful cancer therapeutics that impair DNA repair machinery, leading to an accumulation of DNA damage and consequently cell death. The shared underlying mechanisms driving malignancy and demyelinating disease, together with t...

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Autores principales: Mekhaeil, Marianna, Dev, Kumlesh Kumar, Conroy, Melissa Jane
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8833351/
https://www.ncbi.nlm.nih.gov/pubmed/35158955
http://dx.doi.org/10.3390/cancers14030687
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author Mekhaeil, Marianna
Dev, Kumlesh Kumar
Conroy, Melissa Jane
author_facet Mekhaeil, Marianna
Dev, Kumlesh Kumar
Conroy, Melissa Jane
author_sort Mekhaeil, Marianna
collection PubMed
description SIMPLE SUMMARY: Poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors are successful cancer therapeutics that impair DNA repair machinery, leading to an accumulation of DNA damage and consequently cell death. The shared underlying mechanisms driving malignancy and demyelinating disease, together with the success of anticancer drugs as repurposed therapeutics, makes the repurposing of PARP-1 inhibitors for demyelinating diseases a worthy concept to consider. In addition, PARP-1 inhibitors demonstrate notable neuroprotective effects in demyelinating disorders, including multiple sclerosis which is considered the archetypical demyelinating disease. ABSTRACT: Over the past decade, Poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors have arisen as a novel and promising targeted therapy for breast cancer gene (BRCA)-mutated ovarian and breast cancer patients. Therapies targeting the enzyme, PARP-1, have since established their place as maintenance drugs for cancer. Here, we present existing evidence that implicates PARP-1 as a player in the development and progression of both malignancy and demyelinating disease. These findings, together with the proven clinical efficacy and marketed success of PARP-1 inhibitors in cancer, present the repurposing of these drugs for demyelinating diseases as a desirable therapeutic concept. Indeed, PARP-1 inhibitors are noted to demonstrate neuroprotective effects in demyelinating disorders such as multiple sclerosis and Parkinson’s disease, further supporting the use of these drugs in demyelinating, neuroinflammatory, and neurodegenerative diseases. In this review, we discuss the potential for repurposing PARP-1 inhibitors, with a focus on rare demyelinating diseases. In particular, we address the possible use of PARP-1 inhibitors in examples of rare leukodystrophies, for which there are a paucity of treatment options and an urgent need for novel therapeutic approaches.
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spelling pubmed-88333512022-02-12 Existing Evidence for the Repurposing of PARP-1 Inhibitors in Rare Demyelinating Diseases Mekhaeil, Marianna Dev, Kumlesh Kumar Conroy, Melissa Jane Cancers (Basel) Review SIMPLE SUMMARY: Poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors are successful cancer therapeutics that impair DNA repair machinery, leading to an accumulation of DNA damage and consequently cell death. The shared underlying mechanisms driving malignancy and demyelinating disease, together with the success of anticancer drugs as repurposed therapeutics, makes the repurposing of PARP-1 inhibitors for demyelinating diseases a worthy concept to consider. In addition, PARP-1 inhibitors demonstrate notable neuroprotective effects in demyelinating disorders, including multiple sclerosis which is considered the archetypical demyelinating disease. ABSTRACT: Over the past decade, Poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors have arisen as a novel and promising targeted therapy for breast cancer gene (BRCA)-mutated ovarian and breast cancer patients. Therapies targeting the enzyme, PARP-1, have since established their place as maintenance drugs for cancer. Here, we present existing evidence that implicates PARP-1 as a player in the development and progression of both malignancy and demyelinating disease. These findings, together with the proven clinical efficacy and marketed success of PARP-1 inhibitors in cancer, present the repurposing of these drugs for demyelinating diseases as a desirable therapeutic concept. Indeed, PARP-1 inhibitors are noted to demonstrate neuroprotective effects in demyelinating disorders such as multiple sclerosis and Parkinson’s disease, further supporting the use of these drugs in demyelinating, neuroinflammatory, and neurodegenerative diseases. In this review, we discuss the potential for repurposing PARP-1 inhibitors, with a focus on rare demyelinating diseases. In particular, we address the possible use of PARP-1 inhibitors in examples of rare leukodystrophies, for which there are a paucity of treatment options and an urgent need for novel therapeutic approaches. MDPI 2022-01-29 /pmc/articles/PMC8833351/ /pubmed/35158955 http://dx.doi.org/10.3390/cancers14030687 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Mekhaeil, Marianna
Dev, Kumlesh Kumar
Conroy, Melissa Jane
Existing Evidence for the Repurposing of PARP-1 Inhibitors in Rare Demyelinating Diseases
title Existing Evidence for the Repurposing of PARP-1 Inhibitors in Rare Demyelinating Diseases
title_full Existing Evidence for the Repurposing of PARP-1 Inhibitors in Rare Demyelinating Diseases
title_fullStr Existing Evidence for the Repurposing of PARP-1 Inhibitors in Rare Demyelinating Diseases
title_full_unstemmed Existing Evidence for the Repurposing of PARP-1 Inhibitors in Rare Demyelinating Diseases
title_short Existing Evidence for the Repurposing of PARP-1 Inhibitors in Rare Demyelinating Diseases
title_sort existing evidence for the repurposing of parp-1 inhibitors in rare demyelinating diseases
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8833351/
https://www.ncbi.nlm.nih.gov/pubmed/35158955
http://dx.doi.org/10.3390/cancers14030687
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