ArticleEMBO molecular medicine2021
Loss of PIKfyve drives the spongiform degeneration in prion diseases.
Article in EMBO molecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 42 citations in OpenAlex.
- PrPStem cell reports · 2026Article
- Presymptomatic pharmacological inhibition of mGluR5 improves survival in a mouse model of prion diseases.Acta neuropathologica communications · 2026Article
- One organelle to rule them all: enhancement of lysosomal activity as a therapeutic modality for protein misfolding neurodegenerative diseases.Frontiers in neuroscience · 2026Review
- Autophagy-lysosomal pathway in neurodegeneration.Molecular neurodegeneration advances · 2026Review
- PIKfyve mediates the maturation of mycobacteria-containing vesicles.Frontiers in cellular and infection microbiology · 2026Article
- Disruption of the PIKfyve complex unveils an adaptive mechanism to promote lysosomal repair and mitochondrial homeostasis.Nature communications · 2025Article
- Mechanism of phosphoinositide regulation of lysosomal pH via inhibition of CLC-7.bioRxiv : the preprint server for biology · 2025Article
- Multiomic analyses direct hypotheses for Creutzfeldt-Jakob disease risk genes.Brain : a journal of neurology · 2025Article
- LYVAC/PDZD8 is a lysosomal vacuolator.Science (New York, N.Y.) · 2025Article
- Microglia-specific NF-κB signaling is a critical regulator of prion-induced glial inflammation and neuronal loss.PLoS pathogens · 2025Article
- Exploring immunotherapeutic strategies for neurodegenerative diseases: a focus on Huntington's disease and Prion diseases.Acta pharmacologica Sinica · 2025Review
- Mutant prion protein enhances NMDA receptor activity, activates PKC, and triggers rapid excitotoxicity in mice.The Journal of clinical investigation · 2025Article
- Article
- Rapid and sensitive determination of residual prion infectivity from prion-decontaminated surfaces.mSphere · 2024Article
- A Systematic Review of Sporadic Creutzfeldt-Jakob Disease: Pathogenesis, Diagnosis, and Therapeutic Attempts.Neurology international · 2024Review
- Article
- Review
- Creutzfeldt-Jakob disease and other prion diseases.Nature reviews. Disease primers · 2024Review
- Review
- Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Brain-matter vacuolation is a defining trait of all prion diseases, yet its cause is unknown. Here, we report that prion infection and prion-mimetic antibodies deplete the phosphoinositide kinase PIKfyve-which controls endolysosomal maturation-from mouse brains, cultured cells, organotypic brain slices, and brains of Creutzfeldt-Jakob disease victims. We found that PIKfyve is acylated by the acyltransferases zDHHC9 and zDHHC21, whose juxtavesicular topology is disturbed by prion infection, resulting in PIKfyve deacylation and rapid degradation, as well as endolysosomal hypertrophy and activation of TFEB-dependent lysosomal enzymes. A protracted unfolded protein response (UPR), typical of prion diseases, also induced PIKfyve deacylation and degradation. Conversely, UPR antagonists restored PIKfyve levels in prion-infected cells. Overexpression of zDHHC9 and zDHHC21, administration of the antiprion polythiophene LIN5044, or supplementation with the PIKfyve reaction product PI(3,5)P
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