Disruption of tubulin-alpha4a polyglutamylation prevents aggregation of hyper-phosphorylated tau and microglia activation in mice

Torben Johann Hausrat
University Medical Center Hamburg-Eppendorf
June 1, 2022
Nat Commun
https://pubmed.ncbi.nlm.nih.gov/35858909

This article is currently being updated. View its version on PubMed.

https://pubmed.ncbi.nlm.nih.gov/35858909

Research summary

This study investigates the role of tubulin-alpha4a (Tuba4a) polyglutamylation in tauopathies. Researchers generated a Knockin mouse model with mutations preventing polyglutamylation of Tuba4a. These mice exhibited reduced binding of tau and GSK3 kinase to neuronal microtubules, leading to decreased tau phosphorylation. Crossbreeding with a human tauopathy model reversed tau hyperphosphorylation, oligomerization, and microglial activation, highlighting tubulin polyglutamylation as a potential therapeutic target in tauopathies.

Key outcome of the study

Preventing Tuba4a polyglutamylation reduces tau hyperphosphorylation and microglial activation, suggesting a novel therapeutic approach for tauopathies.

Model

Tuba4aΔpolyGlu Knockin mouse model with point mutations abolishing polyglutamylation of Tuba4a, developed to study the impact on tau pathology.

TARGET:
Tuba4a
Synonyms:
Tubulin alpha-4A chain

Keywords

Tauopathies, Neurodegeneration, Microglial activation, Tubulin modifications

Technical specifications

Knockin model, Point mutations, Polyglutamylation-deficient Tuba4a, Tau pathology assessment

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