Dr. Monica Driscoll to Highlight Extracellular Vesicle–Mediated Aggregate Transfer in the Nervous System | 2026 KKARC Symposium

How do neurons protect themselves from toxic protein buildup? Dr. Monica Driscoll will share research on extracellular vesicle, mediated aggregate transfer at the Herbert and Jacqueline Krieger Klein Alzheimer’s Research Center (KKARC) 2026 Symposium on March 24, 2026. Her talk will focus on exophers, large vesicles that enable neurons to expel harmful proteins and organelles, and their emerging role as a fundamental branch of neuronal proteostasis and stress response. Learn more and register for the symposium before registration closes on March 1.

Talk title: “Modeling Extracellular Vesicle-Mediated Aggregate Transfer in a Living Nervous System”

Abstract:
Proteostasis disruption is a major contributor to neurodegenerative disease and to age-associated decline in cognition. In recent years, the importance of small and large extracellular vesicles in animal health and function has become increasingly apparent. We discovered that C. elegans adult neurons can extrude large vesicles (~5µM, 100X larger than exosomes) that we call exophers. Exophers can carry potentially deleterious proteins and organelles out of the neuron and can hand these materials off to neighboring glial-like cells. Inhibiting chaperone expression, autophagy, or the proteasome, as well as over-expressing aggregating proteins like human AD Ab1-42, expanded polyglutamine Q128 protein, or high concentration mCherry, increases exopher production from the affected neurons. Neurons that express proteotoxic transgenes maintain higher functionality if those neurons produce exophers as compared to those that do not, suggesting that exopher-genesis can be neuroprotective. Recent studies in mammalian models report exopher-like biology in higher organisms, including the human brain. Overall, data converge to support that the mechanism by which an exopher is produced is a likely conserved process that constitutes a fundamental, but formerly unrecognized, branch of neuronal proteostasis and stress response.

We have taken genetic and cell biological approaches to dissecting the mechanisms by which neurons distinguish the garbage they will throw out, how they store threatening material and transport it for extrusion, how the health of the sending neuron is altered by the exopher event, how the extruded exopher is recognized for degradation by a surrounding cell and how exopher-genesis is triggered and regulated. I look forward to sharing our latest findings in my talk.