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【bio-news】用激光摧毁淀粉样蛋白质
Resarchers have found that a technique used to visualize amyloid fibers in the laboratory might have the potential to destroy them in the clinic. The technique involves zapping the fluorescently-tagged fibers with a laser, which can inhibit their growth and degrade them. This study, appearing in this week’s JBC, may offer a non-drug alternative to treat amyloid-based disorders like Alzheimer, Parkinson, and Huntington diseases.
Yuji Goto and colleagues had been studying amyloids, dense tangles of protein, to better understand how they form. In an effort to view amyloid formation under a microscope in real-time, they added an amyloid specific dye called thioflavin T (ThT) to the tangles and then hit it with a laser beam to induce fluorescence. Surprisingly, they found that under the right conditions, the laser could actually stop fiber growth and even degrade the amyloids.
Goto and colleagues believe the laser-excited ThT transfers some of its energy to nearby oxygen, resulting in active oxygen species that alters the surrounding protein fibers. These specific experiments focused on beta2-microglobulin, a major component of amyloids associated with dialysis-related amyloidosis (which currently has no good treatment), though they believe a similar approach of light-induced decompo-sition should work for other types of protein amyloids.
Intermittent laser irradiation
degrades preformed amyloid fibrils
“Destruction of Amyloid Fibrils of a β2-Microglobulin Fragment by Laser Beam Irradiation” by Daisaku Ozawa, Hisashi Yagi, Tadato Ban, Atsushi Kameda, Toru Kawakami, Hironobu Naiki, and Yuji Goto
Article link: http://www.jbc.org/cgi/content/full/284/2/1009
用激光摧毁淀粉样蛋白质
研究者们在实验室中发现了一种能够使淀粉样纤维显影的技术，该技术有可能应用于临床治疗。该技术包括以激光消除荧光标记纤维的方法，它能抑制标记纤维的生长并将其降解。此研究发表于本周的JBC杂志，它可能为治疗淀粉斑引起的疾病，如阿兹海默症、帕金森症以及亨廷顿症提供一种非药物疗法。
Yuji Goto及其同事们致力于研究淀粉斑、蛋白质聚集体，希望能够更好的了解它们的形成机理。在一项显微镜实时检测淀粉斑形成的实验中，他们加入了一种淀粉斑特异性染色剂，名叫硫磺素T（ThT），然后用激光诱导其发出荧光。他们意外的发现，在一定条件下，激光能够停止纤维生长，甚至降解淀粉斑。
Goto及其同事们认为，激光激活ThT时将其能量转移给了周围的氧原子，使氧原子成为激活形式，引起周围蛋白质纤维发生变化。这些特定实验都集中作用于beta2-微球蛋白上，它与透析相关淀粉变（目前尚未有好的治疗方法）共同组成淀粉斑的主要成分之一。研究者们认为，类似的光诱导分解实验可能对其它类型的蛋白质淀粉斑同样起作用。
周期性的激光照射
降解已形成的淀粉纤维 Ozawa D, Yagi H, Ban T, Kameda A, Kawakami T, Naiki H, Goto Y. 2009. Destruction of Amyloid Fibrils of a {beta}2-Microglobulin Fragment by Laser Beam Irradiation. J Biol Chem. 2009 Jan 9;284(2):1009-17. To understand the mechanism by which amyloid fibrils form, we have been making real-time observations of the growth of individual fibrils, using total internal fluorescence microscopy combined with an amyloid-specific fluorescence dye, thioflavin T (ThT). At neutral pH, irradiation at 442 nm with a laser beam to excite ThT inhibited the fibril growth of beta(2)-microglobulin (beta2-m), a major component of amyloid fibrils deposited in patients with dialysis-related amyloidosis. Examination with a 22-residue K3 fragment of beta2-m showed that the inhibition of fibril growth and moreover the destruction of preformed fibrils were coupled with the excitation of ThT. Several pieces of evidence suggest that the excited ThT transfers energy to ground state molecular oxygen, producing active oxygen, which causes various types of chemical modifications. The results imply a novel strategy for preventing the deposition of amyloid fibrils and for destroying preformed amyloid deposits. 这是一种典型的光动力作用，详细的讨论可以参加附件
Liu TCY, Wang YQ, Xu XY, Zhao XF, Hu SJ. 2007. Reactive Oxygen Species Mediated Generalized Photobiomodulation. 2007 IEEE/ICME International Conference on Complex Medical Engineering . 1157-1162. Piscataway NJ, USA: IEEE.
更加详细的讨论，请参见如下帖子中收集的相关帖子
【招聘】激光运动医学招聘博士后
http://www.dxy.cn/bbs/post/view?bid=57&id=3841358&sty=1&tpg=1&ppg=1&age=0#3841358
CME2007_20070317225935.pdf
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作者:admin@医学,生命科学 2011-04-09 17:11
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