Jason Shepherd: The Arc Protein – From Viral Origins to Center Stage in Neuroplasticity and Disease

In this episode I talk with Professor Jason Shepherd about his discoveries concerning a fascinating protein called Arc. In response to synaptic activity Arc levels rapidly increase in postsynaptic dendrites as a result of local translation of the Arc mRNA in the dendrites. Arc plays a critical role in long-term memory although it is not necessary for learning. But perhaps the most interesting twist in the Arc story comes from the Shepherd labs discovery that Arc can self-assemble into highly ordered structures that are essentially identical to the capsids that form the coat of viruses. I talk with Jason about evidence that Arc can bind mRNAs and transfer them from one neuron to another in extracellular vesicles. These findings reveal a whole new mechanism for regulating neuronal network function. Moreover, recently Jason and his lab members have demonstrated a key role for Arc in the trans-neuronal propagation of Tau pathology which is an important advance in understanding how the neurodegenerative process spreads throughout neuronal networks in Alzheimer's disease and other neurodegenerative disorders – and also has implications for novel approaches for halting the disease process.

LINKS:

The Shepherd laboratory page:

https://www.shepherdlab.org/

Key publications from the Shepherd lab:

https://pmc.ncbi.nlm.nih.gov/articles/PMC8041237/pdf/nihms-1661230.pdf

https://www.cell.com/action/showPdf?pii=S0092-8674%2817%2931504-0

https://pmc.ncbi.nlm.nih.gov/articles/PMC11526995/pdf/nihpp-2024.10.22.619703v1.pdf