| http://purl.uniprot.org/citations/23843527 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23843527 | http://www.w3.org/2000/01/rdf-schema#comment | "Mutations in superoxide dismutase 1 (SOD1) cause amyotrophic lateral sclerosis (ALS) in 20% of familial cases (fALS). Mitochondria are one of the targets of mutant SOD1 (mutSOD1) toxicity. We previously demonstrated that at the mitochondria, mutSOD1 forms a toxic complex with Bcl-2, which is then converted into a toxic protein via a structural rearrangement that exposes its toxic BH3 domain (Pedrini et al., 2010). Here we now show that formation of this toxic complex with Bcl-2 is the primary event in mutSOD1-induced mitochondrial dysfunction, inhibiting mitochondrial permeability to ADP and inducing mitochondrial hyperpolarization. In mutSOD1-G93A cells and mice, the newly exposed BH3 domain in Bcl-2 alters the normal interaction between Bcl-2 and VDAC1 thus reducing permeability of the outer mitochondrial membrane. In motor neuronal cells, the mutSOD1/Bcl-2 complex causes mitochondrial hyperpolarization leading to cell loss. Small SOD1-like therapeutic peptides that specifically block formation of the mutSOD1/Bcl-2 complex, recover both aspects of mitochondrial dysfunction: they prevent mitochondrial hyperpolarization and cell loss as well as restore ADP permeability in mitochondria of symptomatic mutSOD1-G93A mice."xsd:string |
| http://purl.uniprot.org/citations/23843527 | http://purl.org/dc/terms/identifier | "doi:10.1523/jneurosci.5385-12.2013"xsd:string |
| http://purl.uniprot.org/citations/23843527 | http://purl.uniprot.org/core/author | "Tan W."xsd:string |
| http://purl.uniprot.org/citations/23843527 | http://purl.uniprot.org/core/author | "Pedrini S."xsd:string |
| http://purl.uniprot.org/citations/23843527 | http://purl.uniprot.org/core/author | "Trotti D."xsd:string |
| http://purl.uniprot.org/citations/23843527 | http://purl.uniprot.org/core/author | "Pasinelli P."xsd:string |
| http://purl.uniprot.org/citations/23843527 | http://purl.uniprot.org/core/author | "Bogush A."xsd:string |
| http://purl.uniprot.org/citations/23843527 | http://purl.uniprot.org/core/author | "Naniche N."xsd:string |
| http://purl.uniprot.org/citations/23843527 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
| http://purl.uniprot.org/citations/23843527 | http://purl.uniprot.org/core/name | "J Neurosci"xsd:string |
| http://purl.uniprot.org/citations/23843527 | http://purl.uniprot.org/core/pages | "11588-11598"xsd:string |
| http://purl.uniprot.org/citations/23843527 | http://purl.uniprot.org/core/title | "Small peptides against the mutant SOD1/Bcl-2 toxic mitochondrial complex restore mitochondrial function and cell viability in mutant SOD1-mediated ALS."xsd:string |
| http://purl.uniprot.org/citations/23843527 | http://purl.uniprot.org/core/volume | "33"xsd:string |
| http://purl.uniprot.org/citations/23843527 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/23843527 |
| http://purl.uniprot.org/citations/23843527 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/23843527 |
| http://purl.uniprot.org/uniprot/#_P10417-mappedCitation-23843527 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23843527 |
| http://purl.uniprot.org/uniprot/#_P08228-mappedCitation-23843527 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23843527 |
| http://purl.uniprot.org/uniprot/#_F2Z471-mappedCitation-23843527 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23843527 |
| http://purl.uniprot.org/uniprot/#_Q3THL7-mappedCitation-23843527 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23843527 |
| http://purl.uniprot.org/uniprot/#_Q8BQK4-mappedCitation-23843527 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23843527 |
| http://purl.uniprot.org/uniprot/#_Q3TIG8-mappedCitation-23843527 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23843527 |
| http://purl.uniprot.org/uniprot/#_Q3U6K8-mappedCitation-23843527 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23843527 |
| http://purl.uniprot.org/uniprot/#_Q60932-mappedCitation-23843527 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23843527 |
| http://purl.uniprot.org/uniprot/#_Q6NTH7-mappedCitation-23843527 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23843527 |