Neuron dysfunction can lead to further glia activation and contribute to further exacerbation of the disease process. The Northwestern researchers found that 188WH and related compounds slowed or reversed the progression of the neuroinflammatory cascade and reduced human amyloid beta-induced glia activation in a mouse specially designed to develop many of the signs of Alzheimer's disease, including neuroinflammation, neuronal and synaptic degeneration and behavioral deficits.
The compound also restored normal levels of markers of synaptic dysfunction in the hippocampus, the area of the brain that helps regulate memory and is gradually destroyed in neurodegenerative diseases such as Alzheimer's. Treatment with the compound also attenuated Alzheimer's-like behavioral deficits in the mice that are due to injury to the hippocampus.
While previous research by the authors and many other investigators in the field has linked plaques, tangles and neuronal injury to synaptic dysfunction and cognitive decline, the direct linkage of glia to these processes and their potential as a selective target for new therapies has not previously been implicated so directly.
There are three key aspects of the report, Watterson said.
"First, a novel compound for development into a new class of Alzheimer's disease therapeutics that target disease has been described. Second, an innovative approach was used for the rapid and cost-effective discovery of orally bioavailable, safe and efficacious compounds, and this approach can be extended to other disease areas," Watterson said.
"Third, the design, synthesis and in vivo analyses we
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Contact: Elizabeth Crown
e-crown@northwestern.edu
312-503-8928
Northwestern University
19-Jan-2006