Research Spotlight: Saving the brain, stopping disease

Healthy neurons Degenerating neurons
Left: The image shows healthy neurons cultured from rats from a part of the brain called the cerebellum.

Right: In degenerating neurons, the oval and bulbous cell bodies shrivel up and fragment, impeding connections with other neurons.

Researchers in SMU’s Dedman College of Humanities and Sciences and The University of Texas at Dallas have identified a group of chemical compounds that slows the degeneration of neurons, a condition that causes such common diseases of old age as Alzheimer’s, Parkinson’s and amyotropic lateral sclerosis (ALS). Their findings are featured in the November 2008 edition of Experimental Biology and Medicine.

SMU Chemistry Professor Edward Biehl and UTD Biology Professor Santosh R. D’Mello teamed to test 45 chemical compounds. Four were found to be the most potent protectors of brain cells, or neurons. The synthesized chemicals, called “3-substituted indolin-2-one compounds,” are derivatives of another compound called GW5074 that was shown to prevent neurodegeneration in a past report published by the D’Mello lab.

While effective at protecting neurons from decay or death, GW5074 is toxic to cells at slightly elevated doses, which makes it unsuitable for clinical testing in patients. The newly identified, second generation compounds maintain the protective feature of GW5074 but are not toxic – even at very high doses – and hold promise in halting the steady march of neurodegenerative diseases like Alzheimer’s and Parkinson’s.

The new compounds may offer doctors an option beyond treating the symptoms of neurodegenerative diseases and may result in compounds that stop cell death that may be used in combination with currently existing drugs that battle the symptoms of brain diseases.

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