Protein discovery may lead to new Alzheimer's drugs

September 06, 2000

An international team of researchers lead by the University of Toronto's Dr. Peter St. George-Hyslop have isolated a key protein involved in the degeneration of nerve cells in Alzheimer's disease, according to a study published in the Sept. 7 issue of Nature.

"We've found a completely unknown protein that's involved in the biochemical processing of the beta-amyloid precursor protein which causes Alzheimer's disease," said lead author Professor Peter St. George-Hyslop, director of the Centre for Research in Neurodegenerative Diseases (CRND) in the University of Toronto's Faculty of Medicine and a neurologist at the University Health Network. "This opens the way for the development of drugs that will target the new protein to manipulate the process that leads to the disease."

St. George-Hyslop and his team named the new protein nicastrin after a small southern Italian village called Nicastro which played an important early role in the discovery of the two genes that cause aggressive early onset forms of Alzheimer's. The researchers isolated nicastrin when they were searching for proteins that adhere to the two proteins, presenilin 1 and presenilin 2, already known to be involved in Alzheimer's. "We set out to find new proteins which bind to the presenilin proteins because mutations in the presenilins cause Alzheimer's disease by inducing abnormal processing of the beta-amyloid precursor protein and the accumulation of a toxic derivative, amyloid beta-peptide, in the brain of patients with Alzheimer's disease," St. George-Hyslop said.

Until now, the exact mechanism by which presenilin mutations altered beta-amyloid precursor protein processing and caused Alzheimer's was unclear. The researchers soon found that nicastrin binds to the beta-amyloid precursor protein and regulates the production of the potentially dangerous amyloid beta-peptide fragment. "More importantly," St. George-Hyslop said, "we discovered a way to manipulate nicastrin to either increase or decrease the production of the harmful amyloid beta-peptide. This could lead to new treatments that will target nicastrin to prevent the overproduction of this neurotoxic protein."

"Nicastrin is clearly a very important component of the cellular machinery underlying Alzheimer's and has several features which suggest that it might be used as a target for the development of new drugs for this disease," said co-author Dr. Paul Fraser of the CRND.

It is not yet clear, St. George-Hyslop said, whether genetic variation in nicastrin is associated with an inherited susceptibility to Alzheimer's disease. In Canada, more than 200,000 people over age 65 have Alzheimer's disease and the Alzheimer Society of Canada estimates that more than 750,000 Canadians will have the disease and related dementias in 30 years. St. George-Hyslop and his research team received international acclaim in 1995 for the discovery of the presenilin genes responsible for the most severe forms of early-onset Alzheimer's. He is the recipient of the Medical Research Council's prestigious Michael Smith Award and was named to Maclean's magazine's 1998 Honor Roll.
Funding was provided by the Canadian Institutes of Health Research, the Alzheimer Society of Ontario, the Howard Hughes Medical Institute, and other international agencies.


Victoria Hadden U of T Public Affairs (416) 978-5948

Megan Easton U of T Public Affairs (416) 978-5949

University of Toronto

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 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