Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gladstone study links Alzheimer’s with toxic protein fragments

16.12.2005


New research from the Gladstone Institute of Neurological Disease details exactly how a mutant form of the protein apolipoprotein E, also known as apoE, is a causative factor for Alzheimer’s disease.



It pinpoints mitochondria, the organelles within cells designed to turn glucose into energy, as a key site that specific fragments of a particular form of apoE attack, leading to the neuronal death characteristic of Alzheimer’s disease (AD).

The findings are published online by the Proceedings of the National Academy of Science, in advance of publication in the December 20, 2005, issue of PNAS.


According to Gladstone Assistant Investigator Yadong Huang, MD, PhD, who headed the study, it has been known for several years that a correlation exists between lowered glucose metabolism and the presence in the brain of a mutant form of a protein that transports cholesterol.

Scientists have been unable to determine if this mutant protein actually interferes with the ability of neurons to make use of glucose in the brain, but they have theorized that such an inability to access glucose might kill off crucial brain cells, causing AD symptoms.

The devastating effects of AD are well known: progressive and inexorable loss of cognitive function that erases memories, extinguishes personality, and robs people of their ability to think, reason and carry out the activities of everyday life. Despite intensive efforts to identify the underlying causes, and considerable progress in unraveling the web of contributing factors, the pathogenesis of AD remains tantalizingly elusive, and a cure is still out of reach, says Huang.

Seeking answers to a fundamental question in AD research on what actually causes brain cells to die in affected patients, Huang and his scientific team pursued a particularly promising avenue of research over the last few years. Their efforts focused on apoE, a protein comprised of 299 amino acids whose apoE4 isoform has been known for the last decade to be the most significant genetic risk factor for AD.

"Several years ago, we found that apoE is subject to cleavage that results in fragments that are toxic to neurons," says Huang, who also is assistant professor of pathology and neurology at UC San Francisco. "This study shows which parts of apoE are toxic and gives hints as to the site of its action."

The research team investigated the cellular and molecular mechanisms of the neurotoxicity caused by apoE4 fragments, performing a series of studies in cultured mouse neuronal cells. The cells expressed apoE fragments of various lengths and with mutations designed to enable the investigators to determine precisely which portions of the fragment--that is, which of apoE4’s 299 amino acids--are responsible for its detrimental effects.

Research findings showed that fragments containing both the lipid- and receptor-binding regions, but lacking the C-terminal 27 amino acids (273-299), were found to be neurotoxic. The toxic fragments appear in the mitochondria, where they impaired membrane integrity and mitochondrial function.

"Blocking interaction of apoE4 fragments with the mitochondria is a potential new strategy for inhibiting the detrimental effects of apoE4 in AD and other neurological diseases," Huang explains.

"Alzheimer’s disease is a complex condition," says co-author Robert W. Mahley, MD, PhD, president of the Gladstone Institutes and UCSF professor of pathology and medicine. "Many factors seem to be involved, and all need to be explored to help us find a way to combat this terrible disease. We are very excited about these particular results because they point to a new and potentially valuable therapeutic strategy."

John Watson | EurekAlert!
Further information:
http://www.gladstone.ucsf.edu
http://www.ucsf.edu

More articles from Studies and Analyses:

nachricht Multi-year study finds 'hotspots' of ammonia over world's major agricultural areas
17.03.2017 | University of Maryland

nachricht Diabetes Drug May Improve Bone Fat-induced Defects of Fracture Healing
17.03.2017 | Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Transport of molecular motors into cilia

28.03.2017 | Life Sciences

A novel hybrid UAV that may change the way people operate drones

28.03.2017 | Information Technology

NASA spacecraft investigate clues in radiation belts

28.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>