Kirsten Young Rose Hills
Investigating the Regulation of Tau Levels
Tau is a microtubule-associated protein that ordinarily regulates cytoskeletal stabilization, but is abnormally hyper-phosphorylated and acetylated in neurodegenerative diseases classed as tauopathies. Although little is known about how tau becomes pathological, previous studies showed that the over-activation of the mTOR pathway could be implicated in tau pathogenesis. Multiple essential cellular functions are regulated by the two different mTOR-dependent pathwaysmTORC1 and mTORC2. These are distinguished from one another by pathway- specific proteins Raptor and Rictor, respectively. To understand which mTOR pathway is responsible for tau pathology, I will generate stable cell lines overexpressing Raptor and Rictor to analyze the effect of upregulation of each independent pathway on tau levels. Understanding tau accumulation mechanistically may help in developing treatments that decrease tau levels and ultimately slow, or even block, neurodegeneration.