Biology and Biomedical Sciences: Neurosciences
Date of Award
Doctor of Philosophy (PhD)
Chair and Committee
Axon loss is a debilitating consequence of a wide range of neurological conditions. As axons degenerate, they go through a stereotyped sequence of morphological changes termed Wallerian degeneration. It has long been hypothesized that there is an active axonal breakdown program, conceptually similar to apoptosis, which underlies Wallerian degeneration. However, the molecular pathways that accomplish this program in neurons have remained elusive. We demonstrate that dual leucine kinase: DLK) promotes degeneration of severed axons in Drosophila and mice, and its target JNK promotes degeneration locally in axons as they commit to degenerate. This pathway also promotes degeneration after chemotherapy exposure, and thus may be a component of a general axon self-destruction program.
Miller, Bradley, "A DLK And JNK Dependent Axon Self-Destruction Program Promotes Wallerian Degeneration" (2011). All Theses and Dissertations (ETDs). 872.