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2020-12-05
[Abstract] Alzheimer’s Disease (AD) has long been associated with accumulation of extracellular amyloid plaques (Aβ) originating from the Amyloid Precursor Protein. Plaques have, however, been discovered in healthy individuals and not all AD brains show plaques, suggesting that extracellular Aβ aggregates may play a smaller role than anticipated. One limitation to studying Aβ peptide in vivo during disease progression is the inability to induce aggregation in a controlled manner. We developed an optogenetic method to induce Aβ aggregation and tested its biological influence in three model organisms–D. melanogaster, C. elegans and D. rerio. We generated a fluorescently labeled, optogenetic Aβ peptide that oligomerizes rapidly in vivo in the presence of blue light ...
[摘要] [摘要]Alzheimer'sdisease(AD)长期以来与淀粉样前体蛋白产生的细胞外淀粉样斑块(Aβ)的积聚有关。然而,在健康人身上发现了斑块,并不是所有的AD大脑都有斑块,这表明细胞外Aβ聚集体的作用可能比预期的要小。在疾病进展过程中研究Aβ肽的一个局限性是无法以可控的方式诱导聚集。我们开发了一种诱导Aβ聚集的光遗传学方法,并在三种模式生物中测试了其生物学效应:D.melanogaster、C.elegans和D.rerio。我们产生了一个荧光标记的,光生的
一种β肽,在所有生物体内,在蓝光存在下迅速寡聚。在这里,我们详细介绍了在动物模型中表达该融合蛋白的程序,使用延时光片显微镜研究对神经系统的影响,并进行代谢分析来测量由于细胞内Aβ聚集而引起的变化。这种方法利用光遗传学来研究AD的病理学,实现了目前任何其他方法都无法实现的体内时空控制。
[背景]阿尔茨海默病(AD)是一种衰弱的、与年龄相关的神经退行性疾病(Zhang等人,2011年;De ...
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