Elucidating how aging impairs brain proteostasis and protein clearance.
Brain health relies on a delicate balance of protein homeostasis, or proteostasis. As we age, the brain becomes less effective at maintaining this balance, leading to toxic protein accumulation that can impair cognitive function and drive neurodegenerative diseases like Alzheimer’s disease. While intracellular quality control systems that degrade proteins are well understood, far less is known about how the brain removes proteins via extrinsic efflux pathways. Dr. Rao’s research investigates how brain-derived proteins are cleared through these drainage pathways, which proteins depend on them, and how their removal is altered by aging. By defining how clearance routes change over time, her work will provide important insight into how aging affects the brain’s ability to maintain a balanced proteome. These insights may not only explain why protein accumulation in the brain occurs during aging but may also reveal new strategies to enhance clearance dynamics to ultimately prevent cognitive decline.
