ArticleMolecular neurodegeneration2023
Multi-modal proteomic characterization of lysosomal function and proteostasis in progranulin-deficient neurons.
Article in Molecular neurodegeneration, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 30 papers.
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30 citing papers in PubMed, 38 citations in OpenAlex.
- Hippocampal neuronal progranulin mediates estrogen‑deficiency‑induced affective vulnerability and lysosomal-autophagic dysfunction.Molecular psychiatry · 2026Article
- Lysosomal homeostasis at the crossroads of neurodegeneration.The Journal of clinical investigation · 2026Review
- UBQLN2 links proteotoxicity with lipid metabolism in neurodegeneration.Nature neuroscience · 2026Article
- Neurodegeneration risk variants promote lysosomal TMEM106B fibril accumulation.bioRxiv : the preprint server for biology · 2026Article
- A Deep Quantitative Proteome Turnover Platform for Human iPSC-derived Neurons.bioRxiv : the preprint server for biology · 2026Article
- Proximity labeling in neuroscience: decoding molecular landscapes for precision neurology.Translational neurodegeneration · 2026Review
- Tau oligomers modulate synapse fate by eliciting progressive bipartite synapse dysregulation and synapse loss.Molecular neurodegeneration · 2026Article
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- Autophagy and mitophagy at the synapse and beyond: implications for learning, memory and neurological disorders.Autophagy · 2026Review
- TDP-43-mediated alternative polyadenylation is associated with a reduction in VPS35 and VPS29 expression in frontotemporal dementia.PLoS biology · 2026Article
- Circular RNA FCHO2 promotes airway remodeling in COPD via regulating nuclear translocation of PTBP1 to repress the splicing of GRN pre-mRNA.Cell death & disease · 2025Article
- The first report of ceroid lipofuscinosis type 11 in China: a novel mutation of GRN and updated clinical review.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Review
- Proteomics Insights Into Lysosome Biogenesis and Maturation.Proteomics · 2025Review
- A specific gene expression program underlies antigen archiving by lymphatic endothelial cells in mammalian lymph nodes.Nature communications · 2025Article
- Article
- Molecular Visualization of Neuronal TDP43 PathologybioRxiv : the preprint server for biology · 2025Article
- Maintenance of neuronal TDP-43 expression requires axonal lysosome transport.bioRxiv : the preprint server for biology · 2025Article
- The antioxidant stress effect of granulin precursor in vitiligo.Scientific reports · 2025Article
- Progranulin's Protective Mechanisms and Therapeutic Potential in Cardiovascular Disease.Cells · 2025Review
- Progranulin deficiency in the brain: the interplay between neuronal and non-neuronal cells.Translational neurodegeneration · 2025Review
Corrections and comments
- Erratum issued
- Update of
Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundProgranulin (PGRN) is a lysosomal glycoprotein implicated in various neurodegenerative diseases, including frontotemporal dementia and neuronal ceroid lipofuscinosis. Over 70 mutations discovered in the GRN gene all result in reduced expression of the PGRN protein. Genetic and functional studies point toward a regulatory role for PGRN in lysosome functions. However, the detailed molecular function of PGRN within lysosomes and the impact of PGRN deficiency on lysosomes remain unclear.
methodsWe developed multifaceted proteomic techniques to characterize the dynamic lysosomal biology in living human neurons and fixed mouse brain tissues. Using lysosome proximity labeling and immuno-purification of intact lysosomes, we characterized lysosome compositions and interactome in both human induced pluripotent stem cell (iPSC)-derived glutamatergic neurons (i
resultsLeveraging the multi-modal proteomics and live-cell imaging techniques, we comprehensively characterized how PGRN deficiency changes the molecular and functional landscape of neuronal lysosomes. We found that PGRN loss impairs the lysosome's degradative capacity with increased levels of v-ATPase subunits on the lysosome membrane, increased hydrolases within the lysosome, altered protein regulations related to lysosomal transport, and elevated lysosomal pH. Consistent with impairments in lysosomal function, GRN-null i
conclusionThis study suggested PGRN as a critical regulator of lysosomal pH and degradative capacity, which influences global proteostasis in neurons. Beyond the study of progranulin deficiency, these newly developed proteomic methods in neurons and brain tissues provided useful tools and data resources for the field to study the highly dynamic neuronal lysosome biology.
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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.