Neurodegenerative diseases, such as Alzheimer’s and Parkinson’s
disease, are associa-
ted with pathological changes in the Tau protein, mainly due to
its hyperphosphorylation.
This work focuses on the influence of post-translational
modifications, mainly phospho-
rylation, on the structure of the Tau protein and their impact
on the fibrillar arrangement
predicted by the AlphaFold 3 (AF3) tool. Experimental
structures were classified into 67
categories, resulting in a Tau fibril catalog. The results
indicate that the reliability of AF3
predictions is the highest in microtubule-related regions. It
was also found that AF3 predicts
structures similar to those associated with corticobasal
degeneration (model 6tjo). Out of
23,446 RMSD comparisons, 87,09 % showed differences smaller
than 5 nm, confirming
the validation of predicted models against experimental
structures and their relevance for
studying neurodegenerative diseases.