Molecular Analysis of Neurotoxin-Induced Apoptosis
Abstract
Apoptosis, a cell death process required for normal brain development, is also aberrantly activated in certain neurodegenerative diseases and following exposure to neurotoxins. We hypothesize that certain components of the signaling pathways activated by 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. We have now confirmed that NF-kappaB is a molecule central to neuronal survival. We have also gathered evidence indicating that p38-alpha activation promotes neuronal death. Furthermore, we provide evidence suggesting that Akt, a serine-thronine kinase believed to be important for the inhibition of apoptosis, is not required for K+ mediated neuronal survival. As a step towards identifying molecules that represent convergent points in the signaling pathways activated by different neurotoxins, we have established conditions for inducing cell-death using two neurotoxins - Beta-amyloid protein and methylmercury.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2001
- Accession Number
- ADA398132
Entities
People
- Santosh D'mello
Organizations
- University of Texas at Dallas