Редактирование: CHMP2B

Charged multivesicular body protein 2b (CHMP2.5) (Chromatin-modifying protein 2b) (CHMP2b) (Vacuolar protein sorting-associated protein 2-2) (Vps2-2) (hVps2-2) [CGI-84]

==Publications==

{{medline-entry
|title=Frontotemporal dementia: insights into the biological underpinnings of disease through gene co-expression network analysis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26912063
|abstract=In frontotemporal dementia (FTD) there is a critical lack in the understanding of biological and molecular mechanisms involved in disease pathogenesis. The heterogeneous genetic features associated with FTD suggest that multiple disease-mechanisms are likely to contribute to the development of this neurodegenerative condition. We here present a systems biology approach with the scope of i) shedding light on the biological processes potentially implicated in the pathogenesis of FTD and ii) identifying novel potential risk factors for FTD. We performed a gene co-expression network analysis of microarray expression data from 101 individuals without neurodegenerative diseases to explore regional-specific co-expression patterns in the frontal and temporal cortices for 12 genes ([[MAPT]], [[GRN]], [[CHMP2B]], [[CTSC]], [[HLA-DRA]], [[TMEM106B]], [[C9orf72]], [[VCP]], [[UBQLN2]], [[OPTN]], [[TARDBP]] and FUS) associated with FTD and we then carried out gene set enrichment and pathway analyses, and investigated known protein-protein interactors (PPIs) of FTD-genes products. Gene co-expression networks revealed that several FTD-genes (such as [[MAPT]] and [[GRN]], [[CTSC]] and [[HLA-DRA]], [[TMEM106B]], and [[C9orf72]], [[VCP]], [[UBQLN2]] and [[OPTN]]) were clustering in modules of relevance in the frontal and temporal cortices. Functional annotation and pathway analyses of such modules indicated enrichment for: i) DNA metabolism, i.e. transcription regulation, DNA protection and chromatin remodelling ([[MAPT]] and [[GRN]] modules); ii) immune and lysosomal processes ([[CTSC]] and [[HLA-DRA]] modules), and; iii) protein meta/catabolism ([[C9orf72]], [[VCP]], [[UBQLN2]] and [[OPTN]], and [[TMEM106B]] modules). PPI analysis supported the results of the functional annotation and pathway analyses. This work further characterizes known FTD-genes and elaborates on their biological relevance to disease: not only do we indicate likely impacted regional-specific biological processes driven by FTD-genes containing modules, but also do we suggest novel potential risk factors among the FTD-genes interactors as targets for further mechanistic characterization in hypothesis driven cell biology work.
|mesh-terms=* Aging
* Animals
* Brain Mapping
* Frontotemporal Dementia
* Gene Regulatory Networks
* Genetic Predisposition to Disease
* Intercellular Signaling Peptides and Proteins
* Mutation
* Risk Factors
* tau Proteins

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4765225
}}
{{medline-entry
|title=Progressive neuronal inclusion formation and axonal degeneration in [[CHMP2B]] mutant transgenic mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/22366797
|abstract=Mutations in the charged multivesicular body protein 2B ([[CHMP2B]]) gene cause frontotemporal lobar degeneration. The mutations lead to C-terminal truncation of the [[CHMP2B]] protein. We generated Chmp2b knockout mice and transgenic mice expressing either wild-type or C-terminally truncated mutant [[CHMP2B]]. The transgenic [[CHMP2B]] mutant mice have decreased survival and show progressive neurodegenerative changes including gliosis and increasing accumulation of p62- and ubiquitin-positive inclusions. The inclusions are negative for the TAR DNA binding protein 43 and fused in sarcoma proteins, mimicking the inclusions observed in patients with [[CHMP2B]] mutation. Mice transgenic for mutant [[CHMP2B]] also develop an early and progressive axonopathy characterized by numerous amyloid precursor protein-positive axonal swellings, implicating altered axonal function in disease pathogenesis. These findings were not observed in Chmp2b knockout mice or in transgenic mice expressing wild-type [[CHMP2B]], indicating that [[CHMP2B]] mutations induce degenerative changes through a gain of function mechanism. These data describe the first mouse model of dementia caused by [[CHMP2B]] mutation and provide new insights into the mechanisms of [[CHMP2B]]-induced neurodegeneration.
|mesh-terms=* Aging
* Animals
* Axons
* Blotting, Western
* Endosomal Sorting Complexes Required for Transport
* Frontotemporal Dementia
* Gliosis
* Humans
* Immunohistochemistry
* Inclusion Bodies
* Introns
* Kaplan-Meier Estimate
* Mice
* Mice, Knockout
* Mice, Transgenic
* Microscopy, Electron
* Nerve Degeneration
* Neurons
* RNA
* Real-Time Polymerase Chain Reaction
* Survival Analysis

|full-text-url=https://sci-hub.do/10.1093/brain/aws006
}}