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Missense mutations of valosin-containing protein (VCP) cause an autosomal dominant disease known as inclusion body myopathy, Paget disease with frontotemporal dementia (IBMPFD) and other neurodegenerative disorders. The pathological mechanism of IBMPFD is not clear and there is no treatment. We show that endogenous VCP negatively regulates Mitofusin, which is required for outer mitochondrial membrane fusion. Because 90% of IBMPFD patients have myopathy, we generated an in vivo IBMPFD model in adult Drosophila muscle, which recapitulates disease pathologies. We show that common VCP disease mutants act as hyperactive alleles with respect to regulation of Mitofusin. Importantly, VCP inhibitors suppress mitochondrial defects, muscle tissue damage and cell death associated with IBMPFD models in Drosophila. These inhibitors also suppress mitochondrial fusion and respiratory defects in IBMPFD patient fibroblasts. These results suggest that VCP disease mutants cause IBMPFD through a gain-of-function mechanism, and that VCP inhibitors have therapeutic value.
Pubmed ID: 28322724
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A commercial antibody supplier and provider of various services.
View all literature mentionsNon-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.
View all literature mentionsA division of Applied Biosystems selling products for the isolation, detection, quantification, amplification, and characterization of RNA.
View all literature mentionsA biorepository and biomaterial supply resource which establishes, verifies, maintains, and distributes cells, cultures and DNA derived from cell cultures to the scientific community around the world. Scientists can browse the sample catalog and request specific cell lines for their research studies. An inventory of the remaining stock of each cell line and DNA preparation is presented in real time. Coriell's significant cell biobank collections include: NIGMS Human Genetic Cell Repository, NINDS Human Genetics DNA and Cell Line Repository, NIA Aging Cell Repository, NHGRI Sample Repository for Human Genetic Research, NEI Age-Related Eye Disease Study (AREDS) Genetic Repository, HD Community BioRepository, American Diabetes Association, GENNID Study, and Autism Research Resource. The repositories are ISO 9000-2001 compliant.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+m*]=Mef2-GAL4.247}3 from BDSC.
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