Protein Glitch May Be Early Problem In Inherited Alzheimer's

August 07, 1996

Johns Hopkins scientists have assembled the first clues to the behavior of presenilin, a protein linked to an inherited form of Alzheimer's disease.

In a report published in the July issue of Neuron, they show that presenilin normally cleaves in two and that a disease-causing mutation in presenilin can prevent the cleavage.

Cleavage is an important change for a protein--it probably has a significant effect on what the protein does. If researchers can find where presenilin cleaves and the enzyme that cleaves it, intervening at this point with drugs or other treatments might be ideal, according to Sangram Sisodia, Ph.D., an associate professor of pathology and neuroscience.

Sisodia and Gopal Thinakaran, Ph.D., David Borchelt, Ph.D., and Michael Lee studied presenilin in cell cultures and in mice that contained copies of the human presenilin gene.

Presenilin is a long protein that snakes in and out of the membranes of nerve cells. It is found in an altered form in nearly 60 percent of all "early onset" familial Alzheimer's disease (FAD) cases, cases where symptoms first appear in patients in their late 20s to the their late 50s.

Because presenilin is present only at very low levels, Sisodia notes, it's unlikely to be directly causing the widespread damage to nerve cells seen in FAD, but it may interfere with other proteins that could. Like dominoes falling, a change in presenilin sets off a chain reaction.

"Think of it as a cascade," says Sisodia. "We don't know how many steps there are in this cascade, but we have a theory about where the cascade is headed."

According to Sisodia, mutated forms of presenilin may influence the formation of plaques in the brain that are among the earliest signs of Alzheimer's disease.

Hopkins researchers currently are looking at mice in which the gene for presenilin is knocked out so that presenilin's function may be revealed by its absence.

Scientists estimate that 15 percent of Alzheimer's patients are FAD victims. A child with one parent with FAD has a 50 percent chance of developing Alzheimer's, a condition characterized by memory loss, dementia, and unusual plaque build-up and nerve cell tangles in the brain. The study also was presented at the recent International Alzheimer's Disease Conference in Osaka, Japan. It was supported by the National Institutes of Health and the National Cancer Institute, the Adler Foundation, the Alzheimer's Association, and the Develbiss Fund.
-end-


Johns Hopkins Medicine

Related Nerve Cells Articles from Brightsurf:

Nerve cells let others "listen in"
How many ''listeners'' a nerve cell has in the brain is strictly regulated.

Nerve cells with energy saving program
Thanks to a metabolic adjustment, the cells can remain functional despite damage to the mitochondria.

Why developing nerve cells can take a wrong turn
Loss of ubiquitin-conjugating enzyme leads to impediment in growth of nerve cells / Link found between cellular machineries of protein degradation and regulation of the epigenetic landscape in human embryonic stem cells

Unique fingerprint: What makes nerve cells unmistakable?
Protein variations that result from the process of alternative splicing control the identity and function of nerve cells in the brain.

Ragweed compounds could protect nerve cells from Alzheimer's
As spring arrives in the northern hemisphere, many people are cursing ragweed, a primary culprit in seasonal allergies.

Fooling nerve cells into acting normal
In a new study, scientists at the University of Missouri have discovered that a neuron's own electrical signal, or voltage, can indicate whether the neuron is functioning normally.

How nerve cells control misfolded proteins
Researchers have identified a protein complex that marks misfolded proteins, stops them from interacting with other proteins in the cell and directs them towards disposal.

The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.

Research confirms nerve cells made from skin cells are a valid lab model for studying disease
Researchers from the Salk Institute, along with collaborators at Stanford University and Baylor College of Medicine, have shown that cells from mice that have been induced to grow into nerve cells using a previously published method have molecular signatures matching neurons that developed naturally in the brain.

Bees can count with just four nerve cells in their brains
Bees can solve seemingly clever counting tasks with very small numbers of nerve cells in their brains, according to researchers at Queen Mary University of London.

Read More: Nerve Cells News and Nerve Cells Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.