Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Proteins linked with Alzheimer's, other neurodegenerative diseases found to clump in normal aging

11.08.2010
In neurodegenerative diseases, clumps of insoluble proteins appear in patients' brains.

These aggregates contain proteins that are unique to each disease, such as amyloid beta in Alzheimer's disease, but they are intertwined with small amounts of many other insoluble proteins that are normally present in a soluble form in healthy young individuals. For years, these other proteins were thought to be accidental inclusions in the aggregates, much as a sea turtle might be caught in a net of fish.

Now, in a surprising new finding, researchers at the University of California, San Francisco, report that many of the proteins present as minor components of disease aggregates actually clump together as a normal part of aging in healthy individuals.

The discovery, in the C. elegans roundworm, refutes a widespread belief that the presence of insoluble proteins is unique to degenerative disease and that the main proteins traditionally associated with each disease (like amyloid beta in Alzheimer's disease) are the only ones that could have an impact.

The research showed that a variety of common soluble proteins, such as those responsible for growth, can become insoluble and form aggregates in animals as they age. Moreover, the research demonstrated that gene manipulations that extend C. elegans lifespan prevent these common proteins from clumping.

The findings appear in the August 11, 2010 issue of the journal PLoS Biology and are freely available online at www.plosbiology.org.

"If you take people with Alzheimer's and look at their aggregates, there are many other proteins in the clump that no one has paid much attention to," said UCSF biochemist Cynthia Kenyon, PhD, director of the Larry L. Hillblom Center for the Biology of Aging at UCSF and senior author of the paper. "It turns out that about half of these proteins are aggregating proteins that become insoluble as a normal part of aging."

The team found that, in the presence of proteins specific to Huntington's disease, these other insoluble proteins actually sped up the course of the disease, indicating that they could be fundamental to its progression.

The findings indicate that widespread protein insolubility and aggregation is an inherent part of aging and that it may influence both lifespan and neurodegenerative disease, Kenyon said.

The presence of insoluble protein aggregates has long been recognized as a hallmark of such neurodegenerative diseases as Alzheimer's, Huntington's and amyotrophic lateral sclerosis (ALS). The team, led by first author Della C. David, PhD, a postdoctoral scholar in the UCSF Department of Biochemistry and Biophysics, asked a simple question that had never been addressed: Do normal proteins form insoluble clumps when normal, healthy individuals age?

They identified roughly 700 proteins in a C. elegans worm that become insoluble as the animal ages. These insoluble proteins are highly over-represented in the aggregates found in human neurodegeneration, the researchers wrote in their paper. They found that many of the proteins that became insoluble were already known to accelerate the aging process and to influence the aggregation of the major disease proteins. Yet even in the healthy aging worms, these proteins had a propensity for clumping and forming hard, rocklike structures.

The team found that this aggregation was significantly delayed or even halted by reducing insulin and IGF-1 hormone activity, whose reduction is known to extend animal lifespan and to delay the progression of Huntington's and Alzheimer's disease in animal models of neurodegenerative diseases.

While there are indisputable differences between worms and men, the roundworm C. elegans (Caenorhabditis elegans) often has led the way in advancing our understanding of human biology, notably in such areas as the mechanism of cell death, insulin pathways, the genes involved in cancer, and aging.

Some of those advances have originated in Kenyon's lab, including the discovery that blocking the activity of a single gene in C. elegans doubled the animal's lifespan. The gene, known as daf-2, encodes a receptor for insulin as well as for IGF-1. The same or related hormone pathways have since been shown to affect lifespan in fruit flies and mice, and are thought to influence lifespan in humans.

Co-authors on the paper include Michael P. Cary, also in the UCSF Department of Biochemistry and Biophysics; Noah Ollikainen, in the UCSF Graduate Program in Biological and Medical Informatics; and Jonathan C. Trinidad and Alma L. Burlingame, both with the Mass Spectrometry Facility in the UCSF Department of Pharmaceutical Chemistry.

The research was supported by fellowships from the Swiss National Foundation and the Larry L. Hillblom Foundation. The work was further supported by the UCSF Program for Breakthrough Biomedical Research and the National Institutes of Health. The authors have declared that no competing interests exist.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. For further information, visit www.ucsf.edu.

Follow UCSF on Twitter at http://twitter.com/ucsfnews

Jennifer O'Brien | EurekAlert!
Further information:
http://www.ucsf.edu

More articles from Life Sciences:

nachricht Warming ponds could accelerate climate change
21.02.2017 | University of Exeter

nachricht An alternative to opioids? Compound from marine snail is potent pain reliever
21.02.2017 | University of Utah

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Start codons in DNA may be more numerous than previously thought

21.02.2017 | Life Sciences

An alternative to opioids? Compound from marine snail is potent pain reliever

21.02.2017 | Life Sciences

Warming ponds could accelerate climate change

21.02.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>