Calcium Modulator Fends Off Alzheimer's

Applied Genetics News, August, 2000

A key protein involved in the regulation of calcium in brain cells may influence the development of therapies and preventive methods for early-onset familial Alzheimer's disease. Malcolm A. Leissring and Frank M. LaFerla, in collaboration with Ian Parker, all of UC Irvine's department of neurobiology and behavior, have discovered that a protein named calsenilin can offset calcium imbalances in brain cells that can lead to the neural changes associated with the disease. Their findings appear in the July 18, 2000 issue of Proceedings of the National Academy of Sciences.

Most early-onset familial Alzheimer's disease cases are triggered by mutations in the genes that produce the protein presenilin. Mutations of presenilin disrupt the proper handling of calcium inside brain cells, which can contribute to the identifying factors of Alzheimer's disease, including development of brain plaques, neural fibril formation, and cell death.

In tests using frog eggs, the UCI team found that calsenilin protein, when bound to specific sites on the presenilin protein, could counteract the effects of mutant presenilin. Calsenilin does this by reversing the increase of calcium signaling caused by presenilin mutations. Researchers from Harvard Medical School and Mount Sinai School of Medicine in New York, who worked with UCI researchers on this study, identified and named this multifunctional protein as one that binds with presenilin in a previous study.

"Our finding provides evidence that calsenilin could be an important mediator of mutant presenilin's effects on calcium signaling," Leissring says. "This could lead to pharmaceutical therapies and preventive measures to offset these mutations and stop the advancement of early-onset familial Alzheimer's disease."