Implications of virus-induced stress granules in tauopathies

TL;DR

This paper reviews how viruses and stress granules may influence tau-related neurodegenerative diseases like Alzheimer's and ALS.

Contribution

The paper identifies 15 stress granule proteins that interact with tau and are involved in viral processes, suggesting a novel link between viral activity and tauopathies.

Findings

Stress granules are proposed as a hub for interactions between tau and viral components.

15 proteins were identified as both tau interactors and participants in viral processes.

The paper highlights both synergistic and protective effects between tau and viruses in neurodegeneration.

Abstract

Tauopathies are characterized by aberrant tau structure and function, which is associated with neurodegenerative dementias, such as Alzheimer’s disease, Pick’s disease, and frontotemporal dementia, as well as the motor neuron disease amyotrophic lateral sclerosis. Consistent association of these neurodegenerative conditions with viruses suggests an interplay between viral activity and the development of tauopathy. In this review, we explore how tau dysregulation may facilitate viral activity, and conversely, how viruses may drive tauopathy. We further discuss how stress granules (SGs) are a likely hub for the interactions between tau and viral components, leading to tau deregulation. Within the network of SG proteins analyzed, 15 proteins were identified to be both tau interactors and implicated in viral processes, having dual functionality. These SG proteins are further discussed in terms of their relationship with tauopathy, viral replication, and neurodegeneration. Concrete examples of synergistic and competing effects between tau and viruses are highlighted, revealing both pathological and protective mechanisms. This dichotomy underscores a complexity that is both disease- and virus-specific, within the context of SG biology and tau pathology. While the viral involvement in tauopathies could be considered detrimental, it may provide insights into antiviral therapeutics to target the accumulation and misfolding of tau in these neurodegenerative diseases.

The online version contains supplementary material available at 10.1186/s40035-026-00538-4.

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