Compounds Suppress Processes Leading to Alzheimer's

A new class of chemicals has been synthesized that suppresses the cellular signaling processes that trigger inflammation of brain cells, a characteristic of Alzheimer's disease, stroke, and other neurodegenerative diseases. The achievement, by researchers from Northwestern University (Evanston, IL, USA) and the University of Louis Pasteur (Strasbourg, France), is described in the January 31, 2002, issue of the Journal of Medicinal Chemistry.

The new compounds inhibit overactivation of glia, cells of the central nervous system that help mount a response to injury or change, but are overactivated in neurodegenerative diseases following traumatic brain injury or stroke. Recent studies suggest that modulating glial inflammation may be an effective therapeutic approach to postponing or slowing progression of neurodegeneration.

The compounds work by mechanisms that are different from inflammatory response enzyme COX-2 (cyclooxygenase) inhibitors and form a new class of experimental anti-inflammatory drugs called p38 kinase inhibitors. They selectively block production of interleukin-1 beta (IL-1B), iNOS (nitric oxide synthase), and nitric oxide by activated glia without diminishing the production of other glial proteins.

"The direct linkage of glial activation to disease pathology underscores the importance of understanding the signal transduction pathways that mediate these critical glial cellular responses and of the need for discovery of cell-permeable drugs that can modulate disease-relevant pathways,” said D. Martin Watterson, professor of molecular biology and biochemistry at Northwestern, who led the study.




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