What is it about?

The protein tau is implicated in several neurodegenerative diseases, including Alzheimer’s disease and related disorders. We previously made a nematode model of neurodegeneration by expressing the human tau protein in nematode neurons. With this model, we identified a previously unknown regulator of tau neurodegeneration, a protein called SPOP. SPOP is a protein involved in protein clearance and is also found in humans. Eliminating the nematode SPOP protein improved behavioral deficits, the accumulation of toxic tau, neurodegeneration, and lifespan. We are now exploring how eliminating SPOP improves our model and if this finding is relevant for human patients.

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Why is it important?

Alzheimer’s disease is a devastating neurodegenerative disease without an effective treatment. Previous research focused on clearing amyloid plagues but overlooked tau tangles. Understanding the role and regulators of tau in disease will be critical to improving patient lives.


Eliminating SPOP also improves a nematode model of a heritable form of the motor neuron disease amyotrophic lateral sclerosis, suggesting SPOP could be important across a number of diseases.

Randall Eck
University of Washington

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This page is a summary of: SPOP loss of function protects against tauopathy, Proceedings of the National Academy of Sciences, December 2022, Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.2207250120.
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