Role of key protein that may stave off inherited form of Alzheimer's disease discovered by UC Irvine researchers

Research on early-onset form of neural disease may lead to prevention methods

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, an inherited form of this neurological disorder that affects adults in their 30s and early 40s, UC Irvine neuroscience researchers have found.

Malcolm A. Leissring and Frank M. LaFerla, in collaboration with Ian Parker, all of UCI'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 Alzheimer's disease. Among its roles, calcium helps regulate numerous cellular activities, but these imbalances, however, are not related to dietary intake of calcium, the UCI researchers point out. 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 in these genes disrupt the proper handling of calcium inside brain cells, which can contribute to the identifying factors of Alzheimer's disease. These pathological features include the development of brain plaques caused by increased production of ß-amyloid proteins, neural fibril formation and cell death.

The UCI researchers have found in tests using frog eggs that the calsenilin protein, when bound to specific sites on the presenilin protein, can counteract the effects of mutant presenilin by stabilizing the activity of the mechanisms, which are called signaling pathways, that distribute calcium within cells. 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 res

Contact: Tom Vasich
University of California - Irvine

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