Transfection of a neuronal cell line with the Wlds gene to further study its neuroprotective phenotype

Axon degeneration can result from primary damage due to a variety of causes, and in some instances, its effects can further propagate damage to vicinal neurons. When an axon has been damaged or transected, Wallerian degeneration is the apoptotic-like mechanism that is initiated, ultimately leading to the death of the neuron. The post-injury cellular inflammatory response is recruited to clear the degraded debris and is also responsible for activating the cascade events leading to additional cell death in surrounding neurons. A unique strain of mutant mice were discovered to express what is called the Wallerian Degeneration Slow (Wld\u27) gene, which produces a chimeric nuclear protein that has been observed to dramatically delay both the onset of axon degeneration and the initiation of the post-injury cellular inflammatory response . Recent studies seem _to indicate the neuroprotective phenotype induced by the Wld\u27 protein is the result of it modulating levels of genetic and protein expression in the damaged neuron. This thesis will review what is known about the Wld\u27 protein and discuss how it offers an in-depth look at the molecular mechanisms behind neurodegenerative injury and disease states. In addition, we will discuss our efforts of isolating and purifying plasmids with the Wld\u27 gene that have been cloned in order to create a stable cell line to aid in the future study for the characterization of neuroprotective mechanisms and the molecular pathways of neurodegeneration