Genetic and pharmacological PARP inhibition reduces axonal degeneration in C. elegans models of ALS
| Autor: | Gilles Tossing, Raphaël Livernoche, Claudia Maios, Constantin Bretonneau, Audrey Labarre, J Alex Parker |
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| Rok vydání: | 2022 |
| Předmět: |
Poly Adenosine Diphosphate Ribose
Ribose Amyotrophic Lateral Sclerosis Neurodegenerative Diseases General Medicine Poly(ADP-ribose) Polymerase Inhibitors MAP Kinase Kinase Kinases Adenosine Diphosphate Genetics Animals Caenorhabditis elegans Caenorhabditis elegans Proteins Molecular Biology Genetics (clinical) |
| Zdroj: | Human Molecular Genetics. 31:3313-3324 |
| ISSN: | 1460-2083 0964-6906 |
| DOI: | 10.1093/hmg/ddac116 |
| Popis: | Axonal degeneration is observed in early stages of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). This degeneration generally precedes apoptosis and therefore may be a promising therapeutic target. An increasing number of genes have been identified to actively regulate axonal degeneration and regeneration; however, only a few potential therapeutic targets have been identified in the context of neurodegenerative diseases. Here we investigate DLK-1, a major axonal regeneration pathway and its contribution to axonal degeneration phenotypes in several Caenorhabditis elegans ALS models. From this pathway, we identified the poly (ADP-ribose) (PAR) polymerases (PARP) PARP-1 and PARP-2 as the most consistent modifiers of axonal degeneration in our models of ALS. Genetic and pharmacological inhibition of PARP-1 and PARP-2 reduces axonal degeneration and improves related motor phenotypes. |
| Databáze: | OpenAIRE |
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