Investigating Tau Function in Stress Granule Formation in hiPSC-derived Neuronal Cell Lines to Model Neurodegenerative Diseases

Undergraduate Honors Thesis

Citations

Citeable URL: https://scholar.colorado.edu/concern/undergraduate_honors_theses/z890rv771

Abstract

Tau, commonly known as a microtubule-associated protein, is implicated in Alzheimer’s disease, frontotemporal dementia, and related tauopathies as its pathological forms create insoluble filaments that accumulate as neurofibrillary tangles. While there has been extensive research conducted on the hyperphosphorylated and pathological forms of tau, a knowledge gap exists in the understanding of the normal tau protein and its multiple functions beyond microtubule binding, especially in bona fide human neural cells. This study employs wild-type (WT) and tau-knockout (Tau-KO) neurons differentiated from human induced pluripotent stem cells (iPSCs) to study the role of tau in the translational cell stress response. Both WT and Tau-KO neurons treated with sodium arsenite form stress granules (SGs), and Tau-KO neurons had slowed resolution of SGs compared to WT cells. The potential interaction of TDP-43 and SGs was also observed in this project, where TDP-43 did not co-localize with G3BP stress granules. The findings presented in this project provide opportunities for further research into the multiplicity of tau function, especially tau’s role in the dynamics of SGs and interactions with their components, elucidating important mechanisms in the pathology of neurodegenerative diseases.

Creator