New research led by Dr. Samuel Young, Jr. reveals that α2δ proteins—key players in brain communication—have far more complex roles than previously believed. This discovery could reshape how we understand and treat conditions like chronic pain, epilepsy, autism, and migraines.
Samuel Young, Jr., PhD, professor and Roper Investigator in the departments of Pediatrics and Pharmacology, and Director of the Center for Molecular Medicine, is senior author on the paper and William Milanick, PhD, postdoc in the Young lab, is first author on the paper published in Neuron: Volume 113, Issue 12, P1886-1897.E9 on June 18, 2025 which describes their findings.
Researchers created a triple knock out mouse line of all three major types of α2δ proteins in the brain, α2δ1, α2δ2, and α2δ3, that would let them to determine which synaptic functions would continue to occur or would not without each of the proteins.
“Young and his team first confirmed that the proteins play several key roles in ensuring that synaptic vesicles with contain neurotransmitters that transmit chemical signals between neurons are delivered at the right place and time to successfully transfer signals from one cell to another.
“Their model was then used to test previous conclusions about the proteins’ roles in creating synapses, synaptic development over time, and the proper organization of neurotransmitter-releasing channels. Researchers found that all of these functions were still being carried out in models that did not have these proteins.”
Researchers also discovered a new role, which is that the loss of those proteins leads to reduced levels another protein, Munc13, mutations of which are related to dementia and AML, amyotrophic lateral schlerosis, a neurodegenerative disease causing muscle weakness and paralysis.
“Young says more research is needed to explore the individual roles of α2δ1, α2δ2, and α2δ3, their regulation of brain function as well as their implications in neurological disorders and the development of therapeutics.”