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Analysis of the involvement of RNA-binding proteins in TAU-dependent neurodegeneration
Ignacio Silva-Llanes1, Pablo Baceiredo-Macho1, Isabel Lastres-Becker2
1Instituto de Investigaciones Biomédicas "Sols-Morreale" CSIC-UAM, Madrid, Spain; Instituto de Investigación Sanitaria La Paz (IdiPaz), Madrid, Spain.
Neurobiology of Disease
|May 21, 2026
Summary
TAU pathology in tauopathies disrupts RNA-binding proteins (RBPs) essential for neuronal function. This RBP dysregulation may contribute to neurodegeneration and synaptic deficits.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Tauopathies are neurodegenerative disorders characterized by pathological TAU protein accumulation.
- TAU protein is crucial for microtubule stability and plays a role in RNA metabolism via RNA-binding proteins (RBPs).
- RBPs regulate mRNA transport, translation, and stress granule (SG) formation, vital for synaptic function.
Purpose of the Study:
- To investigate the hypothesis that TAU pathology dysregulates RBPs involved in RNA transport, translation preinitiation complex (PIC), and SG formation.
- To determine if RBP dysregulation is a common mechanism in tauopathies and linked to impaired TAU function.
Main Methods:
- Analysis of RBP expression (mRNA and protein) in mouse models (AAV-TAU P301L, TAU P301S) and Alzheimer's disease (AD) patient samples.
- Assessment of subcellular localization of RBPs.
Main Results:
- Increased expression of RBPs involved in RNA transport, PIC, and SG formation was observed in mouse models and AD patients.
- Changes in RBP expression occurred at both mRNA and protein levels.
- Altered subcellular localization of some RBPs was noted.
Conclusions:
- RBP dysregulation is a shared mechanism across tauopathies, potentially linked to impaired TAU functionality.
- Upregulation of RBPs might be a compensatory response to synaptic translation deficits in tauopathies.
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