Protein homeostasis is a complex cellular process that regulates protein synthesis and degradation. This homeostatic process is critical for cellular health and the overall health of the organism. The ubiquitin-proteasome system and the autophagolysosome are the primary degraders of aged or misfolded proteins. Impaired functional protein degradation pathways result in the accumulation of misfolded toxic proteins, which have been linked to neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Protein degradation pathways have been extensively studied using single cell models such as yeast. Neurodegenerative diseases, on the other hand, are associated with higher organisms such as humans, where multiple cell types or organs coexist to influence each other. However, it is unclear how the interaction of different cell types or organs influences one’s proteostasis (cell non-autonomous proteostasis). Efforts to elucidate the systemic regulation of proteostasis will aid in the comprehension of the molecular underpinnings of the normal aging process and neurodegenerative diseases. To this end, our lab seeks to understand

1) how systemic inflammation influences neuronal proteostasis in aging and neurodegenerative diseases

2) the role of senescent glial cells in neuronal proteostasis and

3) the molecular basis of tau protein propagation across the brain regions.