Gene editing tests in lab-grown nerve cells reveal how tau protein is controlled

A genome-wide CRISPRi screen identified both known and unexpected pathways that control tau oligomer levels in human neurons.

• Aggregation of the protein tau is linked to neurodegenerative diseases, including Alzheimer's disease and frontotemporal dementia.
• Specific neuronal subtypes exhibit selective vulnerability to tau aggregation and subsequent cell death.
• The E3 ubiquitin ligase CRL5 regulates tau levels by ubiquitinating tau in human neurons.
• Disruption of mitochondrial function may lead to abnormal processing of tau, resulting in disease-related tau fragments.
• Findings highlight potential pathways and therapeutic targets for addressing tauopathies.

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