Albert Einstein College of Medicine researchers led by Ana Maria Cuervo, M.D., Ph.D., and Pablo E Castillo, M.D. Ph.D., have found that seizures can result when a process vital for breaking down and recycling cellular debris becomes defective.

This process, known as chaperone-mediated autophagy (CMA), was discovered by Dr. Cuervo, who has shown that CMA becomes less efficient with age. As a result, toxic molecules can accumulate inside cells, leading to age-related disorders such as Alzheimer’s, Huntington’s, and Parkinson’s disease.

In a new study conducted in mice, Rabia R Khawaja Ph.D., postdoctoral fellow in Dr. Cuervo’s team uncovered a connection between malfunctioning CMA and seizures such as those occurring in epilepsy, brain injury, stroke, and Alzheimer’s. More specifically, the researchers found that CMA directly regulates the excitability of neurons, which—when CMA declines—become hyperexcitable, increasing the risk for seizures. The findings were published online on October 14 in Nature Cell Biology.

“The good news is that this loss of CMA function appears to be reversible,” Dr. Cuervo said. “By boosting CMA activity with genetic enhancements or drug compounds developed here at Einstein, we were able to reduce seizures and improve memory and learning capabilities in mouse models of aging and Alzheimer’s disease. So, CMA appears to be a promising new target for treating seizures associated with epilepsy and other brain disorders.”

An unexpected finding from the study: CMA breaks down different proteins in the synapses (connecting junctions between neurons) of males and females, which may explain why women have more rapid neurodegenerative progression in Alzheimer’s disease and are more vulnerable than men to developing seizures in different brain disorders.

Dr. Cuervo is a distinguished professor of developmental & molecular biology and of medicine, the Robert and Renée Belfer Chair for the Study of Neurodegenerative Diseases, co-director of the Institute for Aging Research, a member of the National Cancer Institute-designated Montefiore Einstein Comprehensive Cancer Center and the Marion Bessin Liver Research Center. The study’s co-leader is Dr. Castillo, the Harold and Muriel Block Chair of Neuroscience and a professor in the Dominick P. Purpura Department of Neuroscience and of psychiatry and behavioral sciences at Einstein.

Albert Einstein College of Medicine holds a portfolio of intellectual property related to this research, including novel composition-of-matter, and is seeking licensing partners to further develop and commercialize this technology. Interested parties can contact the Office of Biotechnology and Business Development at biotech@einsteinmed.edu.