event date: 10 June 2022
The Centre of New Technologies invites to a webinar by
Luca Ferrari, PhD
Max Perutz Labs, Vienna BioCenter, Vienna University, Austria.
Title: Tau degradation by the autophagy machinery
Date: 10th June 2022, Friday
Time: 1:00 pm (Central European Time)
Host: Prof. Krzysztof Kazimierczuk
Zoom link: https://us02web.zoom.us/j/82426581314
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Protein aggregation is a major hallmark of neurodegenerative disorders, Alzheimer’s Disease being the most common one. Alzheimer patients accumulate protein aggregates in the brain: extracellular ABeta and intracellular Tau aggregates.
The autophagy-lysosome system is traditionally associated to removal of bulky substrates, including protein aggregates. The selective removal of protein aggregates is termed aggrephagy; it relies on the condensation of the autophagy cargo receptors p62, NBR1 and TAX1BP1 with a target protein aggregate. Once condensates are formed, they are linked to the downstream autophagy cascade and directed to the lysosome for degradation. In the case of Tau protein, the molecular rules dictating Tau degradation by autophagy, either in its physiological or pathological forms, remain completely obscure.
We deployed a reconstitution approach to shed light on these rules. We showed that monomeric Tau forms condensates with p62, NBR1 and TAX1BP1 only when ubiquitinated. We are now moving toward a pathological scenario by studying condensation of Tau aggregates isolated from post mortem human brains. Our findings may help understanding Tau degradation by autophagy, and its potential harnessing to treat Alzheimer’s Disease.