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2005 Grant - Klann
Identification of Sources of Oxidative Stress in Alzheimer's Disease Model Mice
Eric Klann, Ph.D.
Baylor College of Medicine
2005 Investigator-Initiated Research Grant
Oxidative stress is damage to cellular structures caused by free radicals, or toxic oxygen molecules. Free radicals, normal byproducts of cellular activities, are usually held in check. But oxidative stress appears to be a factor in Alzheimer's disease, and some studies suggests that it may induce the accumulation of beta-amyloid, a tiny protein fragment that is a key suspect in Alzheimer pathology.
One source of free radicals is mitochondria, the energy-producing factories in a cell. Eric Klann, Ph.D., and colleagues have hypothesized that mitochondrial dysfunction causes oxidative stress that subsequently induces beta-amyloid deposits in the Alzheimer brain.
To test this hypothesis, the researchers will cross two lines of genetically altered mice. One line carries a mutated human gene that results in the production of beta-amyloid and the development of an Alzheimer-like disorder. The second line of mice overproduces an antioxidant that essentially eliminates free radicals from mitochondria. The researchers will assess whether, in the absence of the mitochondrial free radicals, the mice develop beta-amyloid deposits, disruptions in cell-to-cell communication or impairments in memory and learning.
Findings from this work may shed light on the earliest events in Alzheimer's disease processes and suggest targets for new drug therapies.