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A new strategy for stroke and Alzheimer’s?

Yale Medicine Magazine, 1998 - Fall


Researchers at the School of Medicine have found that blocking an enzyme known to be involved in cell death could help treat Alzheimer’s disease, Parkinson’s disease, strokes and other age-related neurological diseases.

The findings, published in the Aug. 7 issue of Cell, were the result of observations of mice bred with defective copies of the Caspase-9 gene. The Caspase family of genes plays a role in programmed cell death, called apoptosis, a necessary element of normal biological processes. “The balance between cell production and cell death is important for normal brain development,” said Pasko Rakic, M.D., SC.D., the Dorys McConnell Duberg Professor of Neurobiology. “Too much or too little cell death can cause severe malformations leading to disorders such as mental retardation and childhood epilepsy. This study shows that Caspase-9 is essential for cell death and therefore gives new insight into how the brain develops in normal and pathological conditions.”

In experiments with mice lacking Caspase-9, the investigators found that the absence of the gene blocked neuronal apoptosis. Abnormal activation of cell death is implicated in many human diseases and specific caspases have been linked to a handful of diseases. The research suggests that a therapy could be designed to stop Caspase-9 from triggering apoptosis, thereby blocking cell death linked to certain neurological diseases.

“When mitochondria, the energy factories of cells, are damaged, Caspase-9 is activated, leading to cell death,” said Richard A. Flavell, M.D., professor of immunobiology and biology, and one of the researchers. “In cells lacking Caspase-9 this damage did not give rise to cell death.”

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