 |
|
Structural polymorphism of 441-residue Tau at single residue resolution
February 17, 2009Press release from PLoS Biology
Worldwide almost 30 million suffer from Alzheimer's disease, an irreversible, neurodegenerative condition that is eventually fatal. The brains of people with Alzheimer's contain two types of misfolded proteins - amyloid plaques and tangles of the protein Tau. Whether these protein abnormalities are a cause of Alzheimer's or a consequence of the disease are unclear. A new paper in this week's PLoS Biology investigates the structure of Tau to better understand its role in healthy cells and in the pathology of Alzheimers.
Tau normally functions by binding to microtubules, the building blocks of the cellular skeleton. Microtubules serve as "tracks" for the transport of material within the cell. In patients afflicted by Alzheimer's disease or similar dementia, tau is abnormally altered - it is more phosphorylated. "Our interest was focussed on how certain phosphorylated residues alter the structure of tau in a way that it can not bind to microtubules anymore," explains Markus Zweckstetter at the Max Planck Institute for Biophysical Chemistry.
The failure of previous attempts to analyse the structure of Tau have made it seem mysterious. Standard methods, such as X-ray crystallography, have not revealed the structure. The breakthrough in analysing the structure comes from using Nuclear Magnetic Resonance spectroscopy. The scientists were able to identify the structural properties of tau and follow its fast motions. For the first time detailed investigations of structural changes from a large almost unfolded protein where conducted.
"We can directly observe which modules of the tau protein bind to microtubules. If the protein is equipped with more phosphates than usual we can see that in this case the binding becomes significantly weaker. Tau and microtubule proteins can no longer interact," summarizes Zweckstetter. As a direct consequence the transport along the microtubule "tracks" is disturbed and nerve cell endings do not grow.
Eckhard and Eva Mandelkow at the Max Planck Unit of Structural Molecular Biology in Hamburg are optimistic in using tau as a pharmaceutical target. Using genetically altered mice, Eva Mandelkow and co-workers were able to show reversibility of the fatal consequences of tau aggregation. Next, scientists hope to investigate which inhibitors interact with the tau protein to prevent fibril formation.
http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.1000034
Public Library of Science
The failure of previous attempts to analyse the structure of Tau have made it seem mysterious. Standard methods, such as X-ray crystallography, have not revealed the structure. The breakthrough in analysing the structure comes from using Nuclear Magnetic Resonance spectroscopy. The scientists were able to identify the structural properties of tau and follow its fast motions. For the first time detailed investigations of structural changes from a large almost unfolded protein where conducted.
"We can directly observe which modules of the tau protein bind to microtubules. If the protein is equipped with more phosphates than usual we can see that in this case the binding becomes significantly weaker. Tau and microtubule proteins can no longer interact," summarizes Zweckstetter. As a direct consequence the transport along the microtubule "tracks" is disturbed and nerve cell endings do not grow.
Eckhard and Eva Mandelkow at the Max Planck Unit of Structural Molecular Biology in Hamburg are optimistic in using tau as a pharmaceutical target. Using genetically altered mice, Eva Mandelkow and co-workers were able to show reversibility of the fatal consequences of tau aggregation. Next, scientists hope to investigate which inhibitors interact with the tau protein to prevent fibril formation.
http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.1000034
Public Library of Science
Neurodegenerative Condition Current Events and Neurodegenerative Condition News RSSUmbilical cord blood cell therapy in an animal model of Alzheimer's disease
A novel strategy based on targeted immune suppression using human umbilical cord blood cells may improve the pathology and cognitive decline associated with Alzheimer's disease.
Gene newly linked to inherited ALS may also play role in common dementia
Scientists at Washington University School of Medicine in St. Louis have linked a mutation in a gene known as TDP-43 to an inherited form of amyotrophic lateral sclerosis (ALS), the neurodegenerative condition often called Lou Gehrig's disease.
Learning disabilities associated with language problems later in life
Individuals with a neurodegenerative condition affecting language appear more likely to have had a history of learning disabilities than those with other types of dementia or with no cognitive problems, according to a report in the February issue of Archives of Neurology, one of the JAMA/Archives journals.
Geisinger scientist seeks cure for Lou Gehrig's disease, creating device to find treatment
A small tropical fish, the curiosity of a Geisinger research scientist and some college students have created the perfect storm of sorts in an attempt to find a cure for one of the world's most devastating neurological diseases.
Poor sleep associated with cognitive decline in elderly women
Women who experienced cognitive decline over a 13 to 15 year period after age 65 were more likely to sleep poorly than women whose cognition did not decline.
Cancer researchers add spice to research against rare neuromuscular disease
Scientists who focus on the molecular signaling that underlies prostate cancer have discovered a compound that shows promise against a debilitating neurodegenerative condition known as Kennedy's disease, which is caused by a mutant gene.
More Neurodegenerative Condition Current Events and Neurodegenerative Condition News Articles
 |
Reviews of Physiology, Biochemistry and Pharmacology / Volume 159 by S. G. Amara (Editor), E. Bamberg (Editor), B. Fleischmann (Editor), T. Gudermann (Editor), S. C. Hebert (Editor) |
| © 2009 BrightSurf.com |