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!
Enduring cold temperatures alters fat cell epigenetics
19.04.2018 | University of Tokyo
Full of hot air and proud of it
18.04.2018 | University of Pittsburgh
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.
Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...
In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...
In an article that appears in the journal “Review of Modern Physics”, researchers at the Laboratory for Attosecond Physics (LAP) assess the current state of the field of ultrafast physics and consider its implications for future technologies.
Physicists can now control light in both time and space with hitherto unimagined precision. This is particularly true for the ability to generate ultrashort...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
19.04.2018 | Materials Sciences
19.04.2018 | Physics and Astronomy
19.04.2018 | Physics and Astronomy