Frontotemporal dementia (FTD) is one of the most prevalent forms of early-onset dementia. However, the pathological mechanisms driving neuronal atrophy in FTD remain poorly understood. Here we identify a conserved role for the novel pro-apoptotic protein plenty of SH3s (POSH)/SH3 domain containing ring finger 1 in mediating neuropathology in Drosophila and mammalian models of charged multivesicular body protein 2B (CHMP2BIntron5) associated FTD. Aberrant, AKT dependent, accumulation of POSH was observed throughout the nervous system of both Drosophila and mice expressing CHMP2BIntron5. Knockdown of POSH was shown to be neuroprotective and sufficient to alleviate aberrant neuronal morphology, behavioral deficits and premature-lethality in Drosophila models, as well as dendritic collapse and cell death in CHMP2BIntron5expressing rat primary neurons. POSH knockdown also ameliorated elevated markers of Jun N-terminal kinase and apoptotic cascades in both Drosophila and mammalian models. This study provides the first characterization of POSH as a potential component of an FTD neuropathology, identifying a novel apoptotic pathway with relevance to the FTD spectrum.
Pubmed ID: 29432529 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Proteintech Europe Ltd is an ISO 9001:2008 certified company
View all literature mentionsAn antibody supplier which banks and distributes hybridomas and monoclonal antibodies for use in research. The bank includes antibodies against targets such as GFP, transcription factors, stem cells, and human.
View all literature mentionsDrosophila melanogaster with name w[*]; P{y[+t7.7] w[+mC]=UAS-mCherry.POSH}attP40 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=UAS-myr-Akt.DeltaPH}3/TM3, Sb[1] from BDSC.
View all literature mentionsDrosophila melanogaster with name Canton-S from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118] from BDSC.
View all literature mentionsThis polyclonal targets IgG (H + L)
View all literature mentionsThis polyclonal targets Rabbit IgG (H+L)
View all literature mentionsThis unknown targets Guinea Pig IgG (H+L)
View all literature mentionsThis polyclonal targets SAPK/JNK
View all literature mentionsThis monoclonal targets Glyceraldehyde-3-PDH (GAPDH)
View all literature mentionsThis polyclonal targets Cleaved Caspase-3 (Asp175)
View all literature mentionsThis monoclonal targets Beta Actin
View all literature mentionsThis unknown targets Cleaved Dcp-1 (Asp216)
View all literature mentionsThis unknown targets Akt Substrate, phsopho (Ser / Thr)
View all literature mentionsThis polyclonal targets GFP and GFP Mutant Fusion Proteins Purified 50 ug
View all literature mentionsThis monoclonal targets β-Tubulin III
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsSoftware package used for interactive, or batched, statistical analysis in social science, health sciences and marketing. Software platform offers advanced statistical analysis, a library of machine-learning algorithms, text analysis, open-source extensibility, integration with big data and deployment into applications.Versions that were produced by SPSS Inc. before the IBM acquisition (Versions 18 and earlier) would be given origin or publisher of SPSS Inc. in Chicago.
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsRattus norvegicus with name Crl:WI from RGD.
View all literature mentionsRattus norvegicus with name Crl:WI from RGD.
View all literature mentions