DescriptionThe heat shock response (HSR) provides cytoprotection against protein misfolding and aggregation, characteristic of neurodegenerative diseases. Unfortunately, neurons have a diminished ability to mount this HSR. Understanding the molecular mechanism that limits the activation of heat shock transcription factor 1 (HSF1) is imperative for the development of neurodegenerative disease therapeutics. This thesis provides evidence that SIRT1, a histone deacetylase is required for the activation and stability of HSF1. Our results showed that decreased expression of Sirt1 is a feature of differentiating neural progenitor cells and maturing neurons. In addition, we showed decreased Sirt1 expression results in a decreased amount and activity of HSF1, which contributes to an attenuated HSR. Understanding the regulation and function of HSF1 in neuronal cells, and will expedite advancements in therapeutics development to harness the HSF1-dependent pro-survival mechanism to mitigate disease processes of neurons.