Corporate Banner
Satellite Banner
Proteomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Versatile Proteins Could be New Target for Alzheimer’s Drugs

Published: Monday, September 23, 2013
Last Updated: Sunday, September 22, 2013
Bookmark and Share
NIH-funded discovery began with asking how the brain learns to see.

A class of proteins that controls visual system development in the young brain also appears to affect vulnerability to Alzheimer’s disease in the aging brain.

The proteins, which are found in humans and mice, join a limited roster of molecules that scientists are studying in hopes of finding an effective drug to slow the disease process.

“People are just beginning to look at what these proteins do in the brain. While more research is needed, these proteins may be a brand new target for Alzheimer’s drugs,” said Carla Shatz, Ph.D., the study’s lead investigator.

Dr. Shatz is a professor of biology and neurobiology at Stanford University in California, and the director of Stanford's interdisciplinary biosciences program, BioX.

She and her colleagues report that LilrB2 (pronounced “leer-bee-2”) in humans and PirB (“peer-bee”) in mice can physically partner with beta-amyloid, a protein fragment that accumulates in the brain during Alzheimer’s disease. This in turn triggers a harmful chain reaction in brain cells.

In a mouse model of Alzheimer’s, depleting PirB in the brain prevented the chain reaction and reduced memory loss.

The research was funded in part by the National Eye Institute, the National Institute on Aging (NIA), and the National Institute of Neurological Disorders and Stroke (NINDS), all part of the National Institutes of Health. It is reported in the Sept. 20 issue of Science.

“These findings provide valuable insight into Alzheimer’s, a complex disorder involving the abnormal build-up of proteins, inflammation and a host of other cellular changes,” said Neil Buckholtz, Ph.D., director of the neuroscience division at NIA.

Buckholtz continued, “Our understanding of the various proteins involved, and how these proteins interact with each other, may one day result in effective interventions that delay, treat or even prevent this dreaded disease.”

Alzheimer's disease is the most common cause of dementia in older adults, and affects as many as 5 million Americans.

Large clumps - or plaques - of beta-amyloid and other proteins accumulate in the brain during Alzheimer’s, but many researchers believe the disease process starts long before the plaques appear.

Even in the absence of plaques, beta-amyloid has been shown to cause damage to brain cells and the delicate connections between them.

Dr. Shatz’s discovery took a unique path. She is a renowned neuroscientist, but Alzheimer’s disease is not her focus area. For decades, she has studied plasticity - the brain’s capacity to learn and adapt - focusing mostly on the visual system.

“Dr. Shatz has always been a leader in the field of plasticity, and now she’s taken yet another innovative step - giving us new insights into the abnormal plasticity that occurs in Alzheimer’s disease,” said Michael Steinmetz, Ph.D., a program director at NEI.

Steinmetz continued, “These findings rest squarely on basic research into the development of the visual system.” NEI has funded Dr. Shatz for more than 35 years.

During development, the eyes compete to connect within a limited territory of the brain - a process known as ocular dominance plasticity. The competition takes place during a limited time in early life. If visual experience through one eye is impaired during that time - for example, by a congenital cataract (present from birth) - it can permanently lose territory to the other eye.

“Ocular dominance is a classic example of how a brain circuit can change with experience,” Dr. Shatz said. “We’ve been trying to understand it at a molecular level for a long time.”

Her search eventually led to PirB, a protein on the surface of nerve cells in the mouse brain. She discovered that mice without the gene for PirB have an increase in ocular dominance plasticity.

In adulthood, when the visual parts of their brains should be mature, the connections there are still flexible. This established PirB as a “brake on plasticity” in the healthy brain, Dr. Shatz said.

It wasn’t long before she began to wonder if PirB might also put a brake on plasticity in Alzheimer’s disease. In the current study, she pursued that question with Taeho Kim, Ph.D., a postdoctoral fellow in her lab, and Christopher M. William, M.D., Ph.D., a neuropathology fellow at Massachusetts General Hospital in Boston. Bradley Hyman, M.D., Ph.D., a professor of neurology at Mass General, was a collaborator on the project.

First, the team repeated the genetic experiment that Dr. Shatz had done in normal mice - but this time, they deleted the PirB gene in the Alzheimer’s mice. By about nine months of age, these mice typically develop learning and memory problems. But that didn’t happen in the absence of PirB.

Next, the researchers began thinking about how PirB might fit into the Alzheimer’s disease process, and particularly how it might interact with beta-amyloid. Dr. Kim theorized that since PirB resides on the surface of nerve cells, it might act as a binding site - or receptor - for beta-amyloid. Indeed, he found that PirB binds tightly to beta-amyloid, especially to tiny clumps of it that are believed to ultimately grow into plaques.

Beta-amyloid is known to weaken synapses - the connections between nerve cells. The researchers found that PirB appears to be an accomplice in this process. Without PirB, synapses in the mouse brain were resistant to the effects of beta-amyloid. Other experiments showed that binding between PirB and beta-amyloid can trigger a cascade of harmful reactions that can lead to the breakdown of synapses.

Although PirB is a mouse protein, humans have a closely related protein called LilrB2. The researchers found that this protein also binds tightly to beta-amyloid. By examining brain tissue from people with Alzheimer’s disease, they also found evidence that LilrB2 may trigger the same harmful reactions that PirB can trigger in the mouse brain.

“These are novel results, and direct interaction between beta-amyloid and PirB-related proteins opens up welcome avenues for investigating new drug targets for Alzheimer’s disease,” said Roderick Corriveau, Ph.D., a program director at NINDS.

Dr. Shatz said she hopes to interest other researchers to work on developing drugs to block PirB and LilrB2. Currently, no drugs treat the underlying causes of Alzheimer’s disease.

Most of the interventions that have reached clinical testing are designed to clear away beta-amyloid. To date, only two other beta-amyloid receptors (PrP-C and EphB2) have been found and are being pursued as drug targets.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,300+ scientific posters on ePosters
  • More than 4,900+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Oxygen Can Impair Cancer Immunotherapy
Researchers have identified a mechanism within the lungs where anticancer immune resposnse is inhibited.
Friday, August 26, 2016
New Inflammatory Disease Discovered
NIH researchers have discovered a rare and potentially deadly disease - otulipenia - the mostly affects children.
Tuesday, August 23, 2016
How Parkinson’s Disease Alters Brain Activity Over Time
The NIH study provides a new tool for testing experimental medications aimed at alleviating symptoms and slowing the rate at which the diseases damage the brain.
Tuesday, August 16, 2016
Genetic Cause of Rare Pediatric Neuropathy Identified
NIH mouse study identifies the mechanism responsible for a rare form of pediatric neuropathy.
Thursday, August 04, 2016
Uncovering Rhinovirus C Structure
Researchers have determined the structure of rhinovirus C. Their findings may aid the development of antiviral therapies and vaccines.
Wednesday, July 27, 2016
Advancing Protein Visualization
Cryo-EM methods can determine structures of small proteins bound to potential drug candidates.
Friday, May 27, 2016
Study Finds Factors That May Influence Influenza Vaccine Effectiveness
Researchers at NIH have suggested that the long-held approach to predicting seasonal influenza vaccine effectiveness may need to be revisited.
Wednesday, April 20, 2016
Visualizing a Cancer Drug Target at Atomic Resolution
Using cryo-electron microscopy, researchers were able to view, in atomic detail, the binding of a potential small molecule drug to a key protein in cancer cells.
Wednesday, February 10, 2016
Genomic Signature Shared by Five Types of Cancer
National Institutes of Health researchers have identified a striking signature in tumor DNA that occurs in five different types of cancer.
Monday, February 08, 2016
Natural Protein Points to New Inflammation Treatment
Findings may offer insight to effective treatments for inflammatory diseases, such as rheumatoid arthritis, psoriasis, and multiple sclerosis.
Friday, February 05, 2016
Biomarkers Outperform Symptoms in Parsing Psychosis Subgroups
Multiple biological pathways lead to similar symptoms - NIH-funded study.
Thursday, December 10, 2015
NIH Supports New Studies to Find Alzheimer’s Biomarkers in Down Syndrome
Initiative will track dementia onset, progress in Down syndrome volunteers.
Tuesday, December 01, 2015
Dementia Linked to Deficient DNA Repair
Mutant forms of breast cancer factor 1 (BRCA1) are associated with breast and ovarian cancers but according to new findings, in the brain the normal BRCA1 gene product may also be linked to Alzheimer’s disease.
Tuesday, December 01, 2015
Molecule Proves Key to Brain Repair After Stroke
Scientists found that a molecule known as growth and differentiation factor 10 (GDF10) plays a key role in repair mechanisms following stroke.
Tuesday, November 10, 2015
Nuclear Transport Problems Linked to ALS and FTD
NIH-supported studies point to potential new target for treating neurodegenerative diseases.
Monday, October 19, 2015
Scientific News
Oxygen Can Impair Cancer Immunotherapy
Researchers have identified a mechanism within the lungs where anticancer immune resposnse is inhibited.
Symmetry is Key to Collagen
Researchers describe how symmetry may be the key to growing collagen fibres outside the body.
Breakthrough in GPCR Understanding
Integral Molecular announces breakthrough in understanding the functionality of GPCRs, the largest class of drug targets in human disease.
Designing Ultrasound Tools with Lego-Like Proteins
Study outlines how ultrasound technology can be used for imaging in conjuction with protein engineering.
Enzyme that Triggers Cell Demise in ALS Identified
Scientists from Harvard have identified a key instigator of nerve cell damage in people with amyotrophic lateral sclerosis (ALS).
Molecular Alarm Clock Wakes Resting Ovules
Study of fruit flies yields discovery of a molecular "alarm clock" that activates resting ovules.
Catching Proteins in the Act
Scientists can now observe light activated processes in proteins through the use of free-electron x-ray lasers.
Proteins Preserve Vital Genetic Data
Research has shown how two key proteins bring about the oragnization of chromosomes and our genome.
Signaling Molecule Regulates Release of the Hunger Hormone Ghrelin
Researchers at UT Southwestern have identified that the blocking release of the hormone ghrelin may mediate low blood sugar effect in children taking beta blockers.
Telomere Replenishment in Real Time
Researchers have visualised the process of telomere attachment to chromosomes through single-molecule imaging.
Scroll Up
Scroll Down
Skyscraper Banner

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,300+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,900+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!