Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Scientists Identify Molecular Trigger for Alzheimer’s Disease

Published: Tuesday, May 21, 2013
Last Updated: Tuesday, May 21, 2013
Bookmark and Share
New research establishes nature of malfunction in protein molecules that can lead to onset of dementia.

Researchers have pinpointed a catalytic trigger for the onset of Alzheimer’s disease – when the fundamental structure of a protein molecule changes to cause a chain reaction that leads to the death of neurons in the brain.

For the first time, scientists at Cambridge’s Department of Chemistry have been able to map in detail the pathway that generates “aberrant” forms of proteins which are at the root of neurodegenerative conditions such as Alzheimer’s.

amyloid.gif

Image, magnified a million times, of amyloid fibril, the type of protein structures that are formed in Alzheimer’s.

They believe the breakthrough is a vital step closer to increased capabilities for earlier diagnosis of neurological disorders such as Alzheimer’s and Parkinson’s, and opens up possibilities for a new generation of targeted drugs, as scientists say they have uncovered the earliest stages of the development of Alzheimer’s that drugs could possibly target.  

The study, published today in the journal PNAS, is a milestone in the long-term research established in Cambridge by Professor Christopher Dobson and his colleagues, following the realisation by Dobson of the underlying nature of protein ‘misfolding’ and its connection with disease over 15 years ago. 

The research is likely to have a central role to play in diagnostic and drug development for dementia-related diseases, which are increasingly prevalent and damaging as populations live longer.

“There are no disease modifying therapies for Alzheimer’s and dementia at the moment, only limited treatment for symptoms. We have to solve what happens at the molecular level before we can progress and have real impact,” said Dr Tuomas Knowles, lead author of the study and long-time collaborator of Professor Dobson.

“We’ve now established the pathway that shows how the toxic species that cause cell death, the oligomers, are formed. This is the key pathway to detect, target and intervene – the molecular catalyst that underlies the pathology.” 

In 2010, the Alzheimer’s Research Trust showed that dementia costs the UK economy over £23 billion, more than cancer and heart disease combined. Just last week, PM David Cameron urged scientists and clinicians to work together to “improve treatments and find scientific breakthroughs” to address “one of the biggest social and healthcare challenges we face.”

The neurodegenerative process giving rise to diseases such as Alzheimer’s is triggered when the normal structures of protein molecules within cells become corrupted.

Protein molecules are made in cellular ‘assembly lines’ that join together chemical building blocks called amino acids in an order encoded in our DNA. New proteins emerge as long, thin chains that normally need to be folded into compact and intricate structures to carry out their biological function. 

Under some conditions, however, proteins can ‘misfold’ and snag surrounding normal proteins, which then tangle and stick together in clumps which build to masses, frequently millions, of malfunctioning molecules that shape themselves into unwieldy protein tendrils. 

The abnormal tendril structures, called ‘amyloid fibrils’, grow outwards around the location where the focal point, or 'nucleation' of these abnormal “species” occurs.

Amyloid fibrils can form the foundations of huge protein deposits – or plaques – long-seen in the brains of Alzheimer’s sufferers, and once believed to be the cause of the disease, before the discovery of ‘toxic oligomers’ by Dobson and others a decade or so ago. 

A plaque’s size and density renders it insoluble, and consequently unable to move. Whereas the oligomers, which give rise to Alzheimer's disease, are small enough to spread easily around the brain - killing neurons and interacting harmfully with other molecules - but how they were formed was until now a mystery.

The new work, in large part carried out by researcher Samuel Cohen, shows that once a small but critical level of malfunctioning protein ‘clumps’ have formed, a runaway chain reaction is triggered that multiplies exponentially the number of these protein composites, activating new focal points through ‘nucleation’.

It is this secondary nucleation process that forges juvenile tendrils, initially consisting of clusters that contain just a few protein molecules. Small and highly diffusible, these are the ‘toxic oligomers’ that careen dangerously around the brain cells, killing neurons and ultimately causing loss of memory and other symptoms of dementia. 

The researchers brought together kinetic experiments with a theoretical framework based on master equations, tools commonly used in other areas of chemistry and physics but had not been exploited to their full potential in the study of protein malfunction before.

The latest research follows hard on the heels of another ground breaking study, published in April of this year again in PNAS, in which the Cambridge group, in Collaboration with Colleagues in London and at MIT, worked out the first atomic structure of one of the damaging amyloid fibril protein tendrils. They say the years spent developing research techniques are really paying off now, and they are starting to solve “some of the key mysteries” of these neurodegenerative diseases.

“We are essentially using a physical and chemical methods to address a biomolecular problem, mapping out the networks of processes and dominant mechanisms to ‘recreate the crime scene’ at the molecular root of Alzheimer’s disease,” explained Knowles.

“Increasingly, using quantitative experimental tools and rigorous theoretical analysis to understand complex biological processes are leading to exciting and game-changing results. With a disease like Alzheimer’s, you have to intervene in a highly specific manner to prevent the formation of the toxic agents. Now we’ve found how the oligomers are created, we know what process we need to turn off.”


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 2,900+ scientific posters on ePosters
  • More Than 4,200+ 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

Stem Cells Likely to be Safe for Use in Regenerative Medicine
Cambridge researchers have found the strongest evidence to date that human pluripotent stem cells – cells that can give rise to all tissues of the body – will develop normally once transplanted into an embryo.
Monday, December 21, 2015
The Manufacturing Challenges of Nanotechnology
Head of NanoManufacturing at the Department of Engineering’s Institute for Manufacturing (IfM) Dr Michaël de Volder explains why manufacturing carbon nanotubes is so difficult – and so important.
Thursday, December 03, 2015
Ancient Genome from Africa Sequenced for the First Time
DNA from 4,500-year-old Ethiopian skull reveals a huge migratory wave of West Eurasians into the Horn of Africa around 3,000 years ago had a genetic impact on modern populations right across the African continent.
Monday, October 19, 2015
Greater Understanding Of Polycystic Ovary Syndrome
A new genetic study of over 200,000 women reveals the underlying mechanisms of polycystic ovary syndrome, as well as potential interventions.
Wednesday, September 30, 2015
Maintaining Healthy DNA Delays Menopause
An international study of nearly 70,000 women has identified more than forty regions of the human genome that are involved in governing at what age a woman goes through menopause.
Tuesday, September 29, 2015
New Consortium to Develop and Study Early Stage Drugs
An innovative new Consortium will act as a ‘match-making’ service between pharmaceutical companies and researchers in Cambridge with the aim of developing and studying precision medicines for some of the most globally devastating diseases.
Thursday, July 30, 2015
MRSA Contamination Found in Supermarket Pork
A survey carried out earlier this year has found the first evidence of the ‘superbug’ bacteria Methicillin-Resistant Staphylococcus Aureus (MRSA) in sausages and minced pork obtained from supermarkets in the UK.
Monday, June 22, 2015
Expression of Certain Genes Changes with the Seasons
As the seasons change, so do the expression levels of many human genes, including ones involved in immune function, according to new research.
Thursday, May 14, 2015
Blood Markers Could Help Predict Outcome Of Infant Heart Surgery
New research suggests it may be possible to predict an infant’s progress following surgery for congenital heart disease by analysing a number of important small molecules in the blood.
Friday, May 08, 2015
Poisons, Plants and Palaeolithic Hunters
Dr Valentina Borgia to develop a technique for detecting residues of deadly substances on archaeological objects.
Saturday, April 11, 2015
‘Mini-Lungs’ Grown To Aid The Study Of Cystic Fibrosis
'Mini-lungs’ have been created using stem cells derived from skin cells of patients with cystic fibrosis.
Thursday, March 19, 2015
Gene Discovery Provides Clues To How TB May Evade The Immune System
The largest genetic study of TB susceptibility to date has led to a potentially important new insight into how the pathogen manages to evade the immune system.
Tuesday, March 17, 2015
Human Genome Includes 'Foreign' Genes Not From Our Ancestors
Many animals, including humans, acquired essential ‘foreign’ genes from microorganisms co-habiting their environment in ancient times, according to research published in the open access journal Genome Biology.
Monday, March 16, 2015
Order Matters: Sequence Of Genetic Mutations Determines How Cancer Behaves
The order in which genetic mutations are acquired determines how an individual cancer behaves, according to research from the University of Cambridge, published today in the New England Journal of Medicine.
Thursday, February 12, 2015
Artificially-intelligent Robot Scientist ‘Eve’ Could Boost Search for New Drugs
Eve, an artificially-intelligent ‘robot scientist’ could make drug discovery faster and much cheaper, say researchers writing in the Royal Society journal Interface.
Wednesday, February 04, 2015
Scientific News
Criminal Justice Alcohol Program Linked to Decreased Mortality
Institute has announced that in the criminal justice alcohol program deaths dropped by 4.2 percent over six years.
Charting Kidney Cancer Metabolism
Changes in cell metabolism are increasingly recognized as an important way tumors develop and progress, yet these changes are hard to measure and interpret. A new tool designed by MSK scientists allows users to identify metabolic changes in kidney cancer tumors that may one day be targets for therapy.
Improving Regenerative Medicine
Lab-created stem cells may lack key characteristics, UCLA research finds.
Tick Genome Reveals Secrets of a Successful Bloodsucker
NIH has announced that decipher the genome of the blacklegged tick which could lead to new tick control methods.
"Dark Side" of the Transcriptome
New approach to quantifying gene "read-outs" reveals important variations in protein synthesis and has implications for understanding neurodegenerative diseases.
Individuals' Medical Histories Predicted by their Noncoding Genomes
Researchers have found that analyzing mutations in regions of the genome that control genes can predict medical conditions such as hypertension, narcolepsy and heart problems.
'Molecular Movie' Opens Door to New Cancer Treatments
An international team of scientists led by the University of Liverpool has produced a 'structural movie' revealing the step-by-step creation of an important naturally occurring chemical in the body that plays a role in some cancers.
New Source of Mutations in Cancer
Recently, a new mutation signature found in cancer cells was suspected to have been created by a family of enzymes found in human cells called the APOBEC3 family.
Advancing Synthetic Biology
Living systems rely on a dizzying variety of chemical reactions essential to development and survival. Most of these involve a specialized class of protein molecules — the enzymes.
Madison Researchers Begin Work on Zika Virus
Work will start with basic questions about Zika virus infection.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
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
2,900+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,200+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!