Aaron DiAntonio, M.D., Ph.D
Dr. Aaron DiAntonio is the Alan A. and Edith L. Wolff Professor in the Department of Developmental Biology and co-Director of the Needleman Center for Neurometabolism and Axonal Therapeutics at the Washington University School of Medicine. His laboratory combines genetics, cell biology, biochemistry, and physiology in both Drosophila and mouse to investigate molecular mechanisms that control the formation, maintenance, and repair of neural circuits in development and disease. His laboratory is now translating these fundamental mechanistic insights into novel therapies for the treatment of neurological disease. Dr. DiAntonio is a scientific founder and co-chair of the Scientific Advisory Board for Disarm Therapeutics.
Axon Degeneration: Molecular Mechanisms and Therapeutic Potential
Axon degeneration is an early event contributing to morbidity and progression of neurodegenerative diseases including peripheral neuropathy, multiple sclerosis, ALS, and Parkinson’s disease. Axon degeneration is active program of subcellular destruction, akin to apoptosis but using a distinct molecular program. We have defined a central molecular mechanism driving axon loss in the injured and diseased nervous system, dissecting the central role of the pro-degenerative molecule SARM1. We discovered that SARM1 is the founding member of an evolutionarily conserved family of NAD+ cleaving enzymes and that SARM1 promotes axon degeneration via local disruption of neurometabolism in the axon. The identification of SARM1 as an enzyme is enabling the development of small molecule and gene therapy methods for blocking SARM1 function. We will discuss recent mechanistic insights into the SARM1 axon degeneration pathway and how these new molecular insights may enable the development of novel therapeutics for the prevention and treatment of neurological diseases characterized by axon loss.