Molecular Analysis of Neurotoxin - Induced Apoptosis
Abstract
Apoptosis, a cell-suicide process required for normal brain development, can also be aberrantly triggered in certain neurodegenerative diseases and following exposure to neurotoxins. We hypothesize that certain components of the signaling pathways activated by these different physiological and pathophysiological stimuli might be shared and could serve as targets for the development of therapeutic approaches. In our application, we proposed to compare the signaling pathways activated by four different apoptotic stimuli using cultures of rat cerebellar granule neurons with the goal of identifying common signaling molecules. During the first three years, our goal was to use one of these apoptotic stimuli - potassium (K+) deprivation - and examine the role of four different apoptosis-regulatory molecules. Results obtained over the past year have strengthened our contention that NF-kB is a molecule central to neuronal survival. Other results have shown that the second molecule under study, p38 MAP kinase, affects neuronal survival in a complex manner. Whereas p38-alpha might promote neuronal death, its activity might be neutralized by p38-beta which promotes survival. Apoptosis by K+ deprivation may be due to the decreased p38-beta activity. Finally, our experiments with caspases indicate that these molecules may not be central to the regulation of neuronal apoptosis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2000
- Accession Number
- ADA384860
Entities
People
- Santosh R. D'mello
Organizations
- University of Texas at Dallas