NIH R01 · 2024
A synthetic biology approach for tau post-translational modifications in AD
Oligomeric forms of tau are the primary source of neurotoxicity in a wide range of neurodegenerative diseases. Structural studies of pathological tau aggregates isolated from tauopathy patient brains have uncovered a diversity of disease-specific tau conformations and structural polymorphs, but the mechanism for how they misfold into pathogenic species remains unknown. Here we aim to test a long-standing hypothesis that post- translational modifications (PTMs), such as phosphorylation and acetylation at disease-associated sites, mediate tau oligomerization, structural polymorph-dependent propagation, and neurotoxicity. We propose a bottom-up approach for directly assessing the impact of…
From the public funding record at NIH RePORTER. Describes the funded project, not the reviews below.