Molecular Analysis of the Common Signaling Mechanism of Neuronal Death Induced by Glutamate and Mutated Huntington
Abstract
The goal of this project is to characterized common moledular mechanism of neuronal toxicity mediated by glutamate and polyglutamine-expanded huntingtin. Our results show that activation of mixed-lineage kinase and its down-stream signaling pathway is involved in neuronal toxicity mediated by glutamate and by the mutated huntingtin. We also observed that PSD-95, a scaffold protein that binds to glutamate receptors links glutamate receptor to mixed lineage kinase to induce neuronal toxicity. Moreover, our results also show that normal huntingtin bind and inhibit mixed lineage kinase while polyglutamine-expanded huntingtin loses this important flinction and promotes neuronal toxicity induced by glutamate receptors. Our results indicate that an inhibitor for mixed lineage kinase or C-Jun N-terminal kinase may be beneficial for the prevention of neuronal loss in Huntington's disease and perhaps other neurodegenerative diseases and brain damages induced by acute insult.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2001
- Accession Number
- ADA390035
Entities
People
- Ya F. Liu
Organizations
- Northeastern University