ArticleBrain : a journal of neurology2018
Frontotemporal dementia causative CHMP2B impairs neuronal endolysosomal traffic-rescue by TMEM106B knockdown.
Article in Brain : a journal of neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
33 citing papers in PubMed, 38 citations in OpenAlex.
- Synaptic Proteostasis in Health and Disease.Journal of neurochemistry · 2026Review
- The ALS- and FTD-associated proteins annexin A11 and CHMP2B act sequentially in plasma membrane repair.Developmental cell · 2026Article
- Molecular mechanisms of autophagy-lysosomal pathway dysfunction in neurodegenerative diseases and therapeutic strategies for lysosomal repair: a review.Frontiers in neuroscience · 2026Review
- Molecular Visualization of Neuronal TDP43 PathologybioRxiv : the preprint server for biology · 2025Article
- Amyotrophic Lateral Sclerosis: Focus on Cytoplasmic Trafficking and Proteostasis.Molecular neurobiology · 2025Review
- Axonal transport of CHMP2b is regulated by kinesin-binding protein and disrupted by CHMP2bLife science alliance · 2025Article
- Overexpression of CHMP2B suppresses proliferation of renal clear cell carcinoma cells.Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- The role of autophagy in the pathogenesis and treatment of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).Autophagy reports · 2025Review
- Nuclear pore dysfunction and disease: a complex opportunity.Nucleus (Austin, Tex.) · 2024Review
- The Mechanistic Link Between Tau-Driven Proteotoxic Stress and Cellular Senescence in Alzheimer's Disease.International journal of molecular sciences · 2024Review
- Crucial role of Snf7-3 in synaptic function and cognitive behavior revealed by conventional and conditional knockout mouse models.Neuroscience · 2024Article
- Synaptopathy: presynaptic convergence in frontotemporal dementia and amyotrophic lateral sclerosis.Brain : a journal of neurology · 2024Review
- Physiological and pathological functions of TMEM106B in neurodegenerative diseases.Cellular and molecular life sciences : CMLS · 2024Review
- The endolysosomal pathway and ALS/FTD.Trends in neurosciences · 2023Review
- Superresolution live-cell imaging reveals that the localization of TMEM106B to filopodia in oligodendrocytes is compromised by the hypomyelination-related D252N mutation.Science China. Life sciences · 2023Article
- The identification of high-performing antibodies for Charged multivesicular body protein 2b for use in Western Blot, immunoprecipitation and immunofluorescence.F1000Research · 2023Article
- Astrocyte dysfunction and neuronal network hyperactivity in a CRISPR engineered pluripotent stem cell model of frontotemporal dementia.Brain communications · 2023Article
- The Interplay Between Autophagy and RNA Homeostasis: Implications for Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.Frontiers in cell and developmental biology · 2022Review
- Mendelian and Sporadic FTD: Disease Risk and Avenues from Genetics to Disease Pathways Through In Silico Modelling.Advances in experimental medicine and biology · 2021Article
- Loss of TMEM106B potentiates lysosomal and FTLD-like pathology in progranulin-deficient mice.EMBO reports · 2020Article
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10 authors at 5 institutions in 2 countries.
Funding
Abstract
Mutations in the endosome-associated protein CHMP2B cause frontotemporal dementia and lead to lysosomal storage pathology in neurons. We here report that physiological levels of mutant CHMP2B causes reduced numbers and significantly impaired trafficking of endolysosomes within neuronal dendrites, accompanied by increased dendritic branching. Mechanistically, this is due to the stable incorporation of mutant CHMP2B onto neuronal endolysosomes, which we show renders them unable to traffic within dendrites. This defect is due to the inability of mutant CHMP2B to recruit the ATPase VPS4, which is required for release of CHMP2B from endosomal membranes. Strikingly, both impaired trafficking and the increased dendritic branching were rescued by treatment with antisense oligonucleotides targeting the well validated frontotemporal dementia risk factor TMEM106B, which encodes an endolysosomal protein. This indicates that reducing TMEM106B levels can restore endosomal health in frontotemporal dementia. As TMEM106B is a risk factor for frontotemporal dementia caused by both C9orf72 and progranulin mutations, and antisense oligonucleotides are showing promise as therapeutics for neurodegenerative diseases, our data suggests a potential new strategy for treating the wide range of frontotemporal dementias associated with endolysosomal dysfunction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.