ArticleCell2026
CRISPR screens in iPSC-derived neurons reveal principles of tau proteostasis.
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Article in Cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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36citing papers in PubMed
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Who cites it
36 citing papers in PubMed.
- Disease-specific tau polymorphs are associated with unique protein networks across proteinopathies.The EMBO journal · 2026Article
- Transcriptome changes of disinhibited somatostatin neurons in the medial prefrontal cortex mediating male-specific stress resilience.Research square · 2026Article
- High-Content CRISPR Screening: Methods and Applications.MedComm · 2026Review
- Discovery and Characterization of Inhibitors of Ubiquitin-Like Modifier Activating Enzyme 5 (UBA5): Targeting the UFMylation Pathway in Cancer and Neurodegenerative Diseases.ACS chemical biology · 2026Article
- A massively parallel CRISPR-based screening platform for modifiers of neuronal depolarization.Nature communications · 2026Article
- Article
- APOE4 disrupts the central dogma by arresting neuronal proteome dynamics.bioRxiv : the preprint server for biology · 2026Article
- Recent advances in Alzheimer's disease: From molecular mechanisms to therapeutic strategies.Cell · 2026Review
- Systems genetic dissection of brain gene expression reveals excitotoxic mechanisms of Alzheimer's disease.Molecular psychiatry · 2026Article
- Atypical involvement of Alzheimer's tau proteins in diseases beyond tauopathies.Life medicine · 2026Review
- APOE4 exacerbates glucocorticoid stress hormone-induced tau pathology via mitochondrial dysfunction.Cell death & disease · 2026Article
- Canine Cognitive Dysfunction and Alzheimer's Disease: Pathophysiological Relationships and the Impact of Glymphatic System Impairment on Neurodegeneration.Veterinary sciences · 2026Review
- Optineurin is a gatekeeper of mitochondrial health and proteostasis in Alzheimer's disease vulnerable neurons.bioRxiv : the preprint server for biology · 2026Article
- Promoter mutagenesis and a massively parallel reporter screen of thebioRxiv : the preprint server for biology · 2026Article
- Spatiotemporal transcriptomic profiling reveals upregulation of glycolysis pathway genes before overt tauopathy in the PS19 mouse model.Experimental & molecular medicine · 2026Article
- Prosaposin in CNS health and disease, metabolic stress and exercise adaptation.Journal of molecular medicine (Berlin, Germany) · 2026Review
- The modifier matrix: emerging roles of ubiquitin-like proteins in Alzheimer's disease.Molecular neurodegeneration advances · 2026Review
- Multi-omic phenotyping of MAPT V337M neurons reveals early changes in axonogenesis and tau phosphorylation.NPJ dementia · 2026Article
- Regulators of interferon-responsive microglia uncovered by Genome-wide CRISPRi screening.NPJ dementia · 2026Article
- CUL5-mediated ubiquitination in cancer cell therapy: context-dependent roles, molecular networks, and emerging therapeutic avenues.Frontiers in medicine · 2026Review
Corrections and comments
- Update of
Authors and funding
28 authors.
Avi J SamelsonInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Neurology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Nabeela AriqatInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA 94158, USA.
Justin McKetneyQuantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94158, USA; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94158, USA; Gladstone Institute of Data Science and Biotechnology, Gladstone Institutes, San Francisco, CA 94158, USA.
Gita RohanitazangiInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA 94158, USA.
Celeste Parra BravoInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA 94158, USA; Helen and Robert Appel Alzheimer Disease Research Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA.
Rudra S BoseInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA 94158, USA.
Kyle J TravagliniAllen Institute for Brain Science, Seattle, WA 98103, USA.
Victor L LamDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
Darrin GoodnessInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA 94158, USA.
Thomas TaInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA 94158, USA.
Gary DixonInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA 94158, USA.
Emily MarzetteInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA 94158, USA.
Julianne JinInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA 94158, USA.
Ruilin TianInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA 94158, USA.
Eric TseInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
Romany AbskharonDepartments of Chemistry and Biochemistry and Biological Chemistry, UCLA-DOE Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Henry S PanInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
Emma C CarrollInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Chemistry, San José State University, San José, CA 95192, USA.
Rosalie E LawrenceDepartment of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute UCSF, San Francisco, CA 94158, USA.
Jason E GestwickiInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
Jessica E RexachDepartment of Neurology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
David S EisenbergDepartments of Chemistry and Biochemistry and Biological Chemistry, UCLA-DOE Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Howard Hughes Medical Institute UCLA, Los Angeles, CA 90095, USA.
Nicholas M KanaanDepartment of Translational Neuroscience, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA.
Daniel R SouthworthInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
John D GrossDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
Li GanHelen and Robert Appel Alzheimer Disease Research Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA.
Danielle L SwaneyQuantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94158, USA; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94158, USA; Gladstone Institute of Data Science and Biotechnology, Gladstone Institutes, San Francisco, CA 94158, USA.
Martin KampmannInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: martin.kampmann@ucsf.edu.
Funding
Translational InformaticsP30CA082103 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Alan Ashworth · 1999 to 2026
$209.7MTopographic, cell type and molecular pathway characterization ofAlzheimer's disease using single cell transcriptomics and epigenomicsU19AG060909 · NIA · ALLEN INSTITUTE · PI Jennie Leigh Close, Michael Hawrylycz · 2020 to 2026
$83.6MProject 3U54AI170792 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Yifan Cheng · 2022 to 2026
$35.7MInvestigating regional and cellular vulnerabilities to tau pathology in young-onset Alzheimer's diseaseR01AG075802 · NIA · MAYO CLINIC JACKSONVILLE · PI BERNARDINO Francesco GHETTI, Lea Tenenholz Grinberg · 2022 to 2026
$15.5MProject 3: Autophagy dysfunction and neuronal activity in FTDU54NS100717 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI KOSIK, KENNETH STEPHEN · 2016 to 2020
$10.8MUncovering the Genetic Mechanisms of the Chromosome 17q21.31 Tau Haplotype on Neurodegeneration Risk in FTD and PSPU54NS123746 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHANG, TIMOTHY S · 2021 to 2025
$9.4MClinical Features and Neuropathological Basis of Sleep Wake Behavior in Alzheimer's and PSPR01AG060477 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Lea Tenenholz Grinberg, Thomas C Neylan · 2019 to 2026
$8.2MInterdisciplinary Research Network on Biologically Active Tau Aggregate Polymorphs from Alzheimer's Disease and Related DementiasU24AG072458 · NIA · UNIVERSITY OF TEXAS MED BR GALVESTON · PI EISENBERG, DAVID, KAYED, RAKEZ · 2021 to 2025
$7.8MTowards Treatment of Alzheimer’s Disease by Targeting Pathogenic Tau and Beta-Amyloid StructuresR01AG070895 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DAVID EISENBERG · 2022 to 2026
$5.8MSystematic elucidation of endosomal trafficking as a therapeutic opportunity in AD using CRISPR-based functional genomicsR01AG062359 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KAMPMANN, MARTIN · 2018 to 2022
$3.2MMolecular mechanisms of selective vulnerability of neurons to tauopathyR01AG082141 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CARLO L CONDELLO, Martin Kampmann · 2023 to 2026
$3.0MIdentification of trans-regulatory elements controlling MAPT transcriptionR01AG085357 · NIA · HUDSON-ALPHA INSTITUTE FOR BIOTECHNOLOGY · PI Jesse N Cochran, Richard M Myers · 2024 to 2026
$2.2MNCI NIH HHS P30 CA082103NIAID NIH HHS U54 AI170792NIA NIH HHS F32 AG063487NIA NIH HHS F32 AG076281NIA NIH HHS K99 AG080116NIA NIH HHS R00 AG080116NIA NIH HHS R01 AG060477NIA NIH HHS R01 AG062359NIA NIH HHS R01 AG070895NIA NIH HHS R01 AG075802NIA NIH HHS R01 AG082141NIA NIH HHS R01 AG085357NIA NIH HHS U19 AG060909NIA NIH HHS U24 AG072458NINDS NIH HHS U54 NS100717NINDS NIH HHS U54 NS123746
Abstract
Aggregation of the protein tau defines tauopathies, the most common age-related neurodegenerative diseases, which include Alzheimer's disease and frontotemporal dementia. Specific neuronal subtypes are selectively vulnerable to tau aggregation, dysfunction, and death. However, molecular mechanisms underlying cell-type-selective vulnerability are unknown. To systematically uncover the cellular factors controlling the accumulation of tau aggregates in human neurons, we conducted a genome-wide CRISPRi screen in induced pluripotent stem cell (iPSC)-derived neurons. The screen uncovered both known and unexpected pathways, including UFMylation and GPI anchor biosynthesis, which control tau oligomer levels. We discovered that the E3 ubiquitin ligase CRL5
Indexed as
Induced Pluripotent Stem CellsNeuronsProteostasistau ProteinsCRISPR-Cas SystemsHumansMitochondriaTauopathiesUbiquitinationtau ProteinsCRISPR screenCUL5neurodegenerationprotein aggregationproteostasisSOCS4tau
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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 Socratic graph.