3-substituted indolones as novel therapeutic compounds for neurodegenerative ...( Neurodegenerative diseases such as A...)

Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS), disrupt the quality of life for patients, put a tremendous burden on family caregivers, and cost society billions of dollars annually. The most consistent risk factor for developing neurodegenerative disease is aging. Because of the dramatic increase in life expectancy, the incidence of individuals afflicted with the aging-associated disorders is on the rise representing a major health problem. A commonality shared among this diverse set of disorders is the progressive and relentless loss of certain populations of neurons. Current medications for neurodegenerative diseases alleviate only the symptoms associated with these diseases but do not affect the underlying cause degeneration of neurons. Because neuronal loss continues unabated, such palliative treatments have no effect on disease progression. The identification of small-molecule inhibitors of neuronal death is thus of urgent and critical importance.

In the November issue of EBM, researchers at the University of Texas at Dallas and Southern Methodist University have identified a class of compounds, 3-substituted indolones, that can protect neurons from degeneration. Furthermore, the group has conducted a structure-activity relationship study to identify substituent groups that are important for neuroprotective efficacy. A previous study by the same group demonstrated that one of these 3-substituted indolones, called GW5074, prevents neurodegeneration and improves behavioral outcome in a mouse model of neurodegeneration. The senior author, Dr. Santosh D'Mello said "More recent but unpublished work by our group and Doris Kretzschmar, a collaborator at the Oregon Health and Science University, found that GW5074 and other related 3-substituted indolones are also protective in a fly model of Alzheimer's disease. " The current study identifies several compounds that are more
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