Did I Fall into a Wormhole and Come Out the Other Side with Insights into Alzheimer’s Disease?

  
Insights into disease origins and treatments can come from decades of study chasing down mechanisms to clear pathology, guided by a deep understanding of mechanisms. Alternatively, paths to progress may derive from advances obtained in pursuing fundamental biology whose links to important medical problems or medications had not driven the pursuit. A decade ago, in a quest to understand how the neuronal dopamine transporter (DAT) is regulated in vivo, we reported the identification of a gene in C. elegans whose deletion mimicked the dopamine-dependent synaptic impact of a DAT deletion. Through a series of genetic, biochemical, computational and imaging studies, we now understand that swip-10 is an essential regulator of copper homeostasis, and whose human ortholog, MBLAC1, has been found to be a significant risk factor for a prevalent form of Alzheimer’s disease. Dr. Blakely will describe how findings in a simple worm model, studying the fundamentals of neural signaling, suggest pathways that may present novel opportunities to diminish risk for multiple human neurodegenerative disorders.