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Tau's wanderlust in neurodegenerative diseases

Tauopathies are a group of neurodegenerative diseases caused by the accumulation of abnormal forms of the tau protein. In an unprecedented work made possible by the development of a novel murine model of tauopathy, researchers from the Neurodegenerative Diseases Laboratory (MIRCen/CEA-Jacob/CNRS/Paris-Saclay University) and the INSERM U1172 Alzheimer and Tauopathies Unit (Lille) teamed to show that these abnormal tau proteins migrate from neurons to astrocytes, another type of cell within the brain, and remain toxic in the astrocytes as well. Their study, published 12 April 2021 in the review Brain, suggests that astrocytes too should be considered as therapeutic targets for tau-associated diseases

Published on 12 April 2021

Among the neurodegenerative diseases, tauopathies are defined by the progressive accumulation of aggregates of abnormal tau proteins.

These aggregates are usually found in neurons, the brain cells that fabricate the most tau, which, in normal conditions, stabilizes axonal structures. However, in some tauopathies, these aggregates have been observed in astrocytes as well, although how they develop in those cells and the effects they cause there have remained a mystery. Astrocytes are among the glial cells, which contribute to numerous key functions in the brain, such as trophic factor or neurotransmitter secretion, blood-brain barrier maintenance, or brain lesion repair. But how do tau aggregates develop in these cells and are they toxic in them?

To explore that question, researchers from the Neurodegenerative Diseases Laboratory (LMN; MIRCen/CEA-Jacob/CNRS/Paris-Saclay University) and the INSERM U1172 Alzheimer and Tauopathies Unit (Lille) developed mouse tauopathy models that specifically generate tau aggregate in neurons, and used them to show that tau aggregation in astrocytes can occur secondarily to the pathological aggregation of tau in the neurons. The team also reported that neurons and astrocytes appear able to exchange tau species between them. And finally they determined that, like for neurons, soluble tau species are indeed highly toxic and even fatal for some astrocytes. Astrocytes thus may be not simple bystanders to the clinical symptoms seen in tauopathies, but significant contributors to them.

Indeed, the study published by the LMN-INSERM team in the journal Brain shows that astrocytes intervene in the pathological mechanisms of tauopathies and thus constitute potential targets for the development of novel therapies for neurodegenerative diseases.

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