阿尔兹海默病 z-bo 2020-09-23 339

　　A metal molecule being studied at Rice University begins to glow when it binds to amyloid fibrils implicated in Alzheimer's disease. When the ultraviolet lamp is triggered, this molecule emits brighter light. When such molecules aggregate in laboratory experiments, they can be monitored in real time.

　　Angel Martí, a chemist at Rice University, said: Such a powerful probe may be a boon for researchers seeking a way to crack amyloid plaques, which form in the brains of Alzheimer's patients. . Martí’s laboratory reported on the light switch molecule in the Journal of the American Chemical Society. Rice University graduate student Amir Aliyan is the lead author of this article.

　　Martí and his team studied dyes composed of metal complexes, which emit light when they bind to amyloid fibers or DNA. They found that when the rhenyl dipyridine phenazine compound binds to the amyloid fiber and the ultraviolet light is excited in the test tube, the synthetic molecules increase their natural photon excitation light by several orders of magnitude.

　　Martí said: "Most dyes are photobleached, and their fluorescence will be reduced when they are continuously excited." "This fuel is the exact opposite. Each time it is excited, it can even increase its fluorescence emission." He said, if this metal Molecules float on the solution or are bound to a single amyloid filament, the luminescence effect is hardly so strong.

　　He said that this effect is seen as two stages. The probe incorporates a hydrophobic moiety that naturally binds to the aggregated fibers and emits light. When this combination is formed, it gives the researcher a clear signal that the gathering is taking place.

　　This combination of

　　excitation occurs and the probe is irradiated under ultraviolet rays, which can even increase the light output by more than a hundred times.

　　Rice University researchers suspect that this dramatic increase occurs, that is, when reactive oxygen species attack the amino acids on the β-amyloid fiber, the luminescence of the metal complex will be normally extinguished.

　　Aliyan said: "Our hypothesis is that under ultraviolet light, the reactive oxygen species produced by our (rhenium) metal complexes are more active than traditional molecular oxygen." "There are reports that rhenium complexes can be Activate oxygen, from the formation of an active oxygen to the formation of a more active active oxygen."

　　Martí added: "This is one of our theories." "We still don't understand what happened. But we know that in addition to the increased emission intensity, the complex also chemically modifies the (amyloid) protein."

　　Martí said that experiments to remove as much oxygen as possible eliminated the enhanced fluorescence effect. He said that the laboratory also returned to test an early metal complex based on ruthenium. When this complex was combined with amyloid fiber, it also showed light emission performance. However, it did not show enhanced emission under ultraviolet light.

　　He said: "We thought that this effect might occur when combined with ruthenium, and we missed it completely. So we ran a control experiment, but nothing happened."

　　Martí said: So far, that experiment has made the rhenium complex unique. It also gives researchers the opportunity to learn more about the mechanism of β-amyloid and aggregation.

　　He said: "We have always been interested in knowing where these complexes bind." "If they oxidize β-amyloid protein on the periphery of the binding site, and then by tracking the position of oxidation, we will know where the binding is. Location." This is the so-called footprint method. It will allow us to specifically explore binding and how chemical modifications on the protein surface affect factors like toxicity and aggregation.

　　Aliyan said: When the probes start to aggregate, the probes can perform real-time protein aggregation studies. He said: "It is not obvious to observe with the naked eye." "You need a probe to track this process to see if there is a potential drug that can inhibit the aggregation or make the aggregation formation faster or slower. Then, You can test with or without any drugs, and under various conditions. People would think that if there is a way to modify the accumulation of β-amyloid, there may be a way to treat this process."