Protein Kinase Pathways that Regulate Neuronal Survival and Death
Abstract
Loss of post-mitotic neurons from the adult brain underlies the pathology of neurodegenerative diseases and neurotoxin exposure. Neuronal cell death occurs by two mechanisms; necrosis and apoptosis. Apoptosis is a process whereby developmental cues and environmental stimuli activate a genetic program to implement a series of steps that culminate in cell death. An important aspect of apoptosis is that it can be halted and such interventions may rescue dying neurons. The overall goal of this project is to identify key protein kinases involved in regulating neuronal survival and apoptosis. The aims for the first year of funding, as described in the Statement of Work, were to: (1) Define key protein kinase cascades regulated by neutrophic factors in neurons, and (2) Modulate the protein kinase cascades regulated by neurotrophic factors and determine the consequence on neuronal survival and death. In the last year, we have identified 3 different protein kinases that regulate neuronal survival and a few of the downstream targets of these kinases. We have also shown that treatment of brain grafts with neurotrophic factors or inhibitors of stress-activated protein kinases increase survival of transplanted dopaminergic neurons in hemi-parkinsonian rats. These studies have resulted in 6 published manuscripts and 4 abstracts presented at national scientific meetings.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2000
- Accession Number
- ADA384856
Entities
People
- Kim A. Heidenreich
Organizations
- University of Colorado Health