The tangles, which were first identified in the early 1900s by German psychiatrist and neuropathologist Aloysius Alzheimer, are formed when changes in a protein called tau cause it to aggregate in an insoluble mass in the cytoplasm of cells. Normally, the tau protein is involved in the formation of microtubules, hollow filaments that provide cells with support and structure; abnormal tau tangles, however, cause that structure to break down, and lead to cell death.
Researchers have long puzzled over just what produces the tangles – and, indeed, if they are a cause or a side effect of Alzheimer's and similar neurodegenerative diseases. Now, new research by Eva Chi, an assistant professor of chemical engineering at the University of New Mexico, and her colleagues suggests that changes to the lipid membranes of nerve cells initiate tangle formation.
"Proteins in the brain do not aggregate spontaneously to form amyloid fibrils to cause diseases," says Chi. Rather, she says, "there are physiological triggers that cause these proteins to start aggregating and the lipid membrane may serve such a role." At the AVS Symposium in Nashville, Tenn., held Oct. 30 – Nov. 4, Chi will discuss these tangling triggers and their implications for the development of new Alzheimer's therapies.
Using a combination of techniques, including fluorescence microscopy and X-ray and neutron scattering imaging, Chi and her colleagues found that tau proteins inside nerve cells interact strongly with negatively charged lipids, which are found on the inner surface of cell membranes. "In diseased brains, tau proteins become hyperphosphorylated" – adorned with multiple phosphate (PO43-) groups – "and detach from microtubules. They can then interact with the negatively charged lipids on the cell membrane and start to aggregate into fibrils and cause disease."
When tau proteins interact with the lipid membrane, they can damage the structure of the membrane, "which can possibly make the membranes 'leaky' and cause neurons to die," Chi explains. "There has been much uncertainty about what causes neurodegeneration in these diseases, but now the field is converging on the idea that neuronal death in Alzheimer's disease is caused by the proteins acquiring toxicity as they aggregate."
The researchers suggests that compounds that prevent the proteins from interacting with the lipid membrane – or protect the membrane from being disrupted – could offer hope to Alzheimer's patients. "We are currently looking at how naturally occurring flavonoids [antioxidants found in plants] can protect the cells from protein aggregate-induced toxicity and have found that they reduce protein interaction with membranes," Chi says.
The AVS 58th International Symposium & Exhibition will be held Oct. 30 – Nov. 4 at the Nashville Convention Center.
Presentation NT+AS-WeA8, "Interaction of Alzheimer's Disease Tau Protein with Model Lipid Membranes," is at 4:20 p.m. on Wednesday, Nov. 2.
Main meeting website: http://www2.avs.org/symposium/AVS58/pages/greetings.html
Technical Program: http://www2.avs.org/symposium
Catherine Meyers | EurekAlert!
DNA is held together by hydrophobic forces
23.09.2019 | Chalmers University of Technology
New method for the measurement of nano-structured light fields
23.09.2019 | Westfälische Wilhelms-Universität Münster
How long the battery of your phone or computer lasts depends on how many lithium ions can be stored in the battery's negative electrode material. If the battery runs out of these ions, it can't generate an electrical current to run a device and ultimately fails.
Materials with a higher lithium ion storage capacity are either too heavy or the wrong shape to replace graphite, the electrode material currently used in...
To process information, photons must interact. However, these tiny packets of light want nothing to do with each other, each passing by without altering the...
Researchers from the Department of Atomically Resolved Dynamics of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg, the University of Hamburg and the European Molecular Biology Laboratory (EMBL) outstation in the city have developed a new method to watch biomolecules at work. This method dramatically simplifies starting enzymatic reactions by mixing a cocktail of small amounts of liquids with protein crystals. Determination of the protein structures at different times after mixing can be assembled into a time-lapse sequence that shows the molecular foundations of biology.
The functions of biomolecules are determined by their motions and structural changes. Yet it is a formidable challenge to understand these dynamic motions.
At the International Symposium on Automotive Lighting 2019 (ISAL) in Darmstadt from September 23 to 25, 2019, the Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, a provider of research and development services in the field of organic electronics, will present OLED light strips of any length with additional functionalities for the first time at booth no. 37.
Almost everyone is familiar with light strips for interior design. LED strips are available by the metre in DIY stores around the corner and are just as often...
Later during this century, around 2060, a paradigm shift in global energy consumption is expected: we will spend more energy for cooling than for heating....
19.09.2019 | Event News
10.09.2019 | Event News
04.09.2019 | Event News
23.09.2019 | Life Sciences
23.09.2019 | Materials Sciences
23.09.2019 | Agricultural and Forestry Science