ArticleCommunications biology2021
Genome-wide CRISPR screen identifies protein pathways modulating tau protein levels in neurons.
Article in Communications biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- CRISPR screening in neurodegeneration and lysosomal biology: Uncovering disease mechanisms and genetic modifiers.Molecular genetics and metabolism · 2026Review
- An electrophysiological and proteomics roadmap for human induced glutamatergic neurons: fine-tuning of culture conditions for pathophysiological studies.Cell death discovery · 2026Article
- CRISPR Applications in Alzheimer's Disease: From High-Throughput Genetic Screening to Precision Editing and CNS Delivery.International journal of molecular sciences · 2026Review
- Article
- A HaloTag-4R-Tau Pulse-Chase Sensor Reveals Neddylation Inhibition Promotes Degradation of Tau in iNeurons.bioRxiv : the preprint server for biology · 2026Article
- CRISPR-based functional genomic screening in neurodegeneration: mechanistic insights into AD, PD, and ALS.Frontiers in aging neuroscience · 2026Review
- CRISPR/Cas9-Based therapeutics as a promising strategy for management of Alzheimer's disease: progress and prospects.Frontiers in cellular neuroscience · 2025Review
- Article
- CRISPR-based genetic screens in human pluripotent stem cells derived neurons and brain organoids.Cell and tissue research · 2025Review
- Genome-scale CRISPR-Cas9 screening in stem cells: theories, applications and challenges.Stem cell research & therapy · 2024Review
- CRISPRi: a way to integrate iPSC-derived neuronal models.Biochemical Society transactions · 2024Review
- Strategies for translating proteomics discoveries into drug discovery for dementia.Neural regeneration research · 2024Review
- Understanding neural development and diseases using CRISPR screens in human pluripotent stem cell-derived cultures.Frontiers in cell and developmental biology · 2023Review
- Towards elucidating disease-relevant states of neurons and glia by CRISPR-based functional genomics.Genome medicine · 2022Review
- CRISPR/Cas9-based genome-wide screening of Dictyostelium.Scientific reports · 2022Article
- Altered Cerebrospinal Fluid Exosomal microRNA Levels in Young-Onset Alzheimer's Disease and Frontotemporal Dementia.Journal of Alzheimer's disease reports · 2021Article
Corrections and comments
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Authors and funding
21 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aggregates of hyperphosphorylated tau protein are a pathological hallmark of more than 20 distinct neurodegenerative diseases, including Alzheimer's disease, progressive supranuclear palsy, and frontotemporal dementia. While the exact mechanism of tau aggregation is unknown, the accumulation of aggregates correlates with disease progression. Here we report a genome-wide CRISPR screen to identify modulators of endogenous tau protein for the first time. Primary screens performed in SH-SY5Y cells, identified positive and negative regulators of tau protein levels. Hit validation of the top 43 candidate genes was performed using Ngn2-induced human cortical excitatory neurons. Using this approach, genes and pathways involved in modulation of endogenous tau levels were identified, including chromatin modifying enzymes, neddylation and ubiquitin pathway members, and components of the mTOR pathway. TSC1, a critical component of the mTOR pathway, was further validated in vivo, demonstrating the relevance of this screening strategy. These findings may have implications for treating neurodegenerative diseases in the future.
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Registered trials
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