A disintegrin-metalloproteinase prevents amyloid plaque formation and hippocampal defects in an Alzheimer disease mouse model
Alzheimer Disease (AD), a progressive neurological disorder, is characterized by the presence of amyloid plaques in the brain. These plaques are comprised of aggregates of amyloid beta-peptides (AB peptides), which are believed to play a central role in disease development. Most strategies to prevent AD have been aimed at reducing the generation of amyloid beta-peptides. This is done by targeting specific enzymes, beta- and gamma-secretase, in the amyloid precursor protein (APP) degradation pathway, which sequentially cleave APP to form the Ab peptide. Falk Fahrenholz and colleagues at the University of Mainz, Germany, now provide evidence that targeting and alternative enzyme, alpha-secretase, might be a useful alternative strategy for reducing AB peptide. In the APP processing pathway, alpha-secretase cleavage of APP generates an alternative breakdown product of the protein that cannot generate AB peptide. Here the researchers use a mouse model deficient in or over expressing the gene ADAM10, which codes for alpha-secretase protein. In these studies, they find that moderate increased expression of ADAM10 in mice reduced AB peptide formation, prevented plaque formation, and, from a functional standpoint provided improvement in both long-term potentiation and cognitive impairment. On the other hand, mice lacking ADAM10 had increased number and size of amyloid plaques. The data here provide evidence that a-secretase might be a useful therapeutic target for AD, and also suggest that impairment of this enzyme might underlie some forms of the disease.
An accompanying commentary by Christian Haas and Stefan F. Lichtenthaler provides details on the APP degradation pathway and places this work and AD in this context.
Investigators may unlock mystery of how staph cells dodge the body's immune system
22.09.2017 | Cedars-Sinai Medical Center
Monitoring the heart's mitochondria to predict cardiac arrest?
21.09.2017 | Boston Children's Hospital
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
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