| http://purl.uniprot.org/citations/36239430 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/36239430 | http://www.w3.org/2000/01/rdf-schema#comment | "Sarm1 is an evolutionary conserved innate immune adaptor protein that has emerged as a primary regulator of programmed axonal degeneration over the past decade. In vitro structural insights have revealed that although Sarm1 induces energy depletion by breaking down nicotinamide adenine dinucleotide+ (NAD+ ), it is also allosterically inhibited by NAD+ . However, how NAD+ levels modulate the activation of intracellular Sarm1 has not been elucidated so far. This study focuses on understanding the events leading to Sarm1 activation in both neuronal and non-neuronal cells using the mitochondrial complex I inhibitor rotenone. Here, we report the regulation of rotenone-induced cell death by loss of NAD+ that may act as a 'biological trigger' of Sarm1 activation. Our study revealed that early loss of endogenous NAD+ levels arising due to PARP1 hyperactivation preceded Sarm1 induction following rotenone treatment. Interestingly, replenishing NAD+ levels by the PARP inhibitor, PJ34 restored mitochondrial complex I activity and also prevented subsequent Sarm1 activation in rotenone-treated cells. These cellular data were further validated in Drosophila melanogaster where a significant reduction in rotenone-mediated loss of locomotor abilities, and reduced dSarm expression was observed in the flies following PARP inhibition. Taken together, these observations not only uncover a novel regulation of Sarm1 induction by endogenous NAD+ levels but also point towards an important understanding on how PARP inhibitors could be repurposed in the treatment of mitochondrial complex I deficiency disorders."xsd:string |
| http://purl.uniprot.org/citations/36239430 | http://purl.org/dc/terms/identifier | "doi:10.1111/febs.16652"xsd:string |
| http://purl.uniprot.org/citations/36239430 | http://purl.uniprot.org/core/author | "Sarkar A."xsd:string |
| http://purl.uniprot.org/citations/36239430 | http://purl.uniprot.org/core/author | "Chakraborty S."xsd:string |
| http://purl.uniprot.org/citations/36239430 | http://purl.uniprot.org/core/author | "Dutta S."xsd:string |
| http://purl.uniprot.org/citations/36239430 | http://purl.uniprot.org/core/author | "Dey P."xsd:string |
| http://purl.uniprot.org/citations/36239430 | http://purl.uniprot.org/core/author | "Mukherjee P."xsd:string |
| http://purl.uniprot.org/citations/36239430 | http://purl.uniprot.org/core/author | "Sur M."xsd:string |
| http://purl.uniprot.org/citations/36239430 | http://purl.uniprot.org/core/date | "2023"xsd:gYear |
| http://purl.uniprot.org/citations/36239430 | http://purl.uniprot.org/core/name | "FEBS J"xsd:string |
| http://purl.uniprot.org/citations/36239430 | http://purl.uniprot.org/core/pages | "1596-1624"xsd:string |
| http://purl.uniprot.org/citations/36239430 | http://purl.uniprot.org/core/title | "Early loss of endogenous NAD+ following rotenone treatment leads to mitochondrial dysfunction and Sarm1 induction that is ameliorated by PARP inhibition."xsd:string |
| http://purl.uniprot.org/citations/36239430 | http://purl.uniprot.org/core/volume | "290"xsd:string |
| http://purl.uniprot.org/citations/36239430 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/36239430 |
| http://purl.uniprot.org/citations/36239430 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/36239430 |
| http://purl.uniprot.org/uniprot/#_A0A6M3Q7S1-mappedCitation-36239430 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/36239430 |
| http://purl.uniprot.org/uniprot/#_A8JNN1-mappedCitation-36239430 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/36239430 |
| http://purl.uniprot.org/uniprot/#_A8JNN2-mappedCitation-36239430 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/36239430 |
| http://purl.uniprot.org/uniprot/#_A8JNN3-mappedCitation-36239430 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/36239430 |
| http://purl.uniprot.org/uniprot/#_M9NFP2-mappedCitation-36239430 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/36239430 |
| http://purl.uniprot.org/uniprot/#_P35875-mappedCitation-36239430 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/36239430 |
| http://purl.uniprot.org/uniprot/#_M9NE45-mappedCitation-36239430 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/36239430 |
| http://purl.uniprot.org/uniprot/#_M9PHR5-mappedCitation-36239430 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/36239430 |
| http://purl.uniprot.org/uniprot/#_Q6IDD9-mappedCitation-36239430 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/36239430 |