LipReleaseTau
The pathological deposition in the central nervous system of aggregated forms of tau protein into paired helical filaments (PHFs) and neurofibrillary tangles (NFTs) is a hallmark of numerous Tauopathies. These severe neurological disorders (over 20) include Alzheimer’s disease (AD) and frontotemporal dementia. Emerging evidence supports that the spreading of toxic disease-associated tau conformations from cell-to-cell (in a prion-like mechanism) is critical for the progression of Tauopathies. This frontier project is focused on describing the first steps of the unconventional secretion of pathological tau, namely its plasma membrane recruitment and self-assembly in synthetic/reconstituted vesicles, and finally in SH-SY5Y cells. Our team is employing advanced microscopy techniques (mainly at the single-molecule level) to describe the physical/structural features of the transient oligomeric species responsible for membrane translocation. Altogether, this project will provide a foundation for the development of novel therapeutic approaches and inhibitors to mitigate tau spreading.
Project webpage Start year 01/03/2023 End year 31/08/2024 ID 2022.01454.PTDC iBB Role Coordinator iBB Budget 49 889,70 € Research Group BSIRG PI Ana Melo Project Partners n.a. Status Ongoing Funding FCT