Neurotrophin Therapy of Neurodegenerative Disorders with Mitochondrial Dysfunction
Abstract
This research program will determine whether accelerated neuron death due to increased oxidative stress resulting from mitochondrial dysfunction can be compensated or corrected by neurotrophin stimulation. The experiments will be carried out in two models of mitochondrial dysfunction. 1)hippocampal neurons from the trisomy 16 mouse, which undergo increased apoptosis and have a mitochondrial defect, that has now been identified as a decrease in Complex I-mediated respiration and 2)neurons chronically treated with the neurotoxin rotenone to induce a defect in mitochondrial function. 0.1-0.5 nM rotenone treatment has now been shown to leave hippocampal neurons vulnerable to a second oxidative stress. A unique aspect of this approach is that the neuronal responsiveness to brain derived neurotrophic factor (BDNF) will be enhanced by overexpressing the BDNF receptor via an andenovirus vector, resulting in an increase in sensitivity to BDNF. Such neurons would be expected to have an enhanced survival response to endogenous BDNF and may be more resistant to oxidative stress characteristic of Parkinson's disease and other neurodegenerative disorders.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2004
- Accession Number
- ADA434706
Entities
People
- Linda L. Bambrick
Organizations
- University of Maryland, Baltimore