ArticleEMBO reports2020
Loss of TMEM106B and PGRN leads to severe lysosomal abnormalities and neurodegeneration in mice.
Article in EMBO reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 109 citations in OpenAlex.
- Article
- Lysosomal dysfunction in neurodegenerative disease.Nature reviews. Neurology · 2026Review
- TGF-β signaling promotes astroglial activation and TDP-43 proteinopathy in organoid models of frontotemporal lobar degeneration.The Journal of clinical investigation · 2026Article
- Neuroinflammation-induced downregulation of RAB7 in murine astrocytes disrupts endo-lysosomal homeostasis and induces astrogliosis.Cell communication and signaling : CCS · 2026Article
- TMEM106B C-terminal fragments drive nucleocytoplasmic transport failure and TDP-43 mislocalization in the aging human brain.bioRxiv : the preprint server for biology · 2026Article
- Axon Initial Segment: Structure, Biological Functions, Diseases, and Therapeutic Targets.MedComm · 2026Review
- Neurodegeneration risk variants promote lysosomal TMEM106B fibril accumulation.bioRxiv : the preprint server for biology · 2026Article
- Granulin loss and TMEM106B risk converge on lysosomal C-terminal fragment pathology in frontotemporal dementia.bioRxiv : the preprint server for biology · 2026Article
- Analyses of plasma multi-omic data across ancestries identify novel pathways implicated in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Mitochondria and Lipid Defects in Hereditary Progranulin-Related Frontotemporal Dementia.Cells · 2026Article
- The cGAS-STING Pathway in Dementia: An Emerging Mechanism of Neuroinflammation.Brain sciences · 2025Review
- Molecular Visualization of Neuronal TDP43 PathologybioRxiv : the preprint server for biology · 2025Article
- Divergent and convergent TMEM106B pathology in murine models of neurodegeneration and human disease.Acta neuropathologica communications · 2025Article
- Disease-modifying effects of TMEM106B in genetic frontotemporal dementia: a longitudinal GENFI study.Brain : a journal of neurology · 2025Article
- The role of endolysosomal progranulin and TMEM106B in neurodegenerative diseases.Molecular neurodegeneration · 2025Review
- Mendelian randomization identifies proteins involved in neurodegenerative diseases.Brain : a journal of neurology · 2025Article
- PGRN as an emerging regulator of lipid metabolism in neurodegenerative diseases.Communications biology · 2025Review
- Challenges of modelling TDP-43 pathology in mice.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Review
- Increased TMEM106B levels lead to lysosomal dysfunction which affects synaptic signaling and neuronal health.Molecular neurodegeneration · 2025Article
- Progranulin deficiency in the brain: the interplay between neuronal and non-neuronal cells.Translational neurodegeneration · 2025Review
10 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Haploinsufficiency of progranulin (PGRN) is a leading cause of frontotemporal lobar degeneration (FTLD). Loss of PGRN leads to lysosome dysfunction during aging. TMEM106B, a gene encoding a lysosomal membrane protein, is the main risk factor for FTLD with PGRN haploinsufficiency. But how TMEM106B affects FTLD disease progression remains to be determined. Here, we report that TMEM106B deficiency in mice leads to accumulation of lysosome vacuoles at the distal end of the axon initial segment in motor neurons and the development of FTLD-related pathology during aging. Ablation of both PGRN and TMEM106B in mice results in severe neuronal loss and glial activation in the spinal cord, retina, and brain. Enlarged lysosomes are frequently found in both microglia and astrocytes. Loss of both PGRN and TMEM106B results in an increased accumulation of lysosomal vacuoles in the axon initial segment of motor neurons and enhances the manifestation of FTLD phenotypes with a much earlier onset. These results provide novel insights into the role of TMEM106B in the lysosome, in brain aging, and in FTLD pathogenesis.
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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.