Human .alpha. synuclein expressing transgenic mice
In methods for screening treatments for, and treatment of, neurodegenerative diseases, aggregation in neurons of NACP/.alpha.-synuclein is measured and expression of a non-amyloidogenic protein is stimulated in order to reduce the level aggregration. For purposes of screening agents for treatment of neurodegenerative disease, oxidative stress in the neuronal cells is stimulated by introducing a mixture of metal-ions and hydrogen peroxide. Examples of appropriate metals include iron, aluminum, and copper. After introduction of the agent under evaluation for stimulation of expression of non-amyloidogenic protein, the effectiveness is measured by testing for a decrease in the level of aggregation of NACP/.alpha.-synuclein. In an exemplary embodiment, the non-amyloidogenic protein is .beta.-synuclein. The aggregation of NACP/.alpha.-synuclein is dependent upon the concentration of metal ions in the neuronal cells. In addition, the presence of chelating agents appears to modulate the build-up of NACP/.alpha.-synuclein aggregates which are responsible for synaptic and neuronal dysfunction.
Masliah; Eliezer (San Diego, CA), Hashimoto; Makoto (La Jolla, CA), Rockenstein; Edward (Chula Vista, CA), Mucke; Lennart (San Francisco, CA)
The Regents of the University of California (Oakland, CA)
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