Forloni G
Biology of Neurodegenerative Disorders Laboratory, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
Curr Opin Neurol. 1996 Dec;9(6):492-500. doi: 10.1097/00019052-199612000-00017.
Neuropathological observations, supported by genetic and biochemical studies, indicate the central role of amyloid-beta protein deposits in the pathogenesis of Alzheimer's disease. In prion-related encephalopathies also, an altered form of prion protein forms amyloid fibrils and accumulates in the brain. In both conditions the amyloid deposition is accompanied by nerve cell loss, the pathogenesis and molecular basis of which are not understood. Synthetic peptides homologous to amyloid-beta protein and its fragments and to prion protein fragments are utilized to investigate the mechanisms of cerebral deposit formation and the role played by these proteins in Alzheimer's disease and prion-related encephalopathies, respectively. Amyloid-beta protein peptides have been shown to be neurotoxic and amyloidogenic under experimental conditions and numerous studies have been performed to clarify the mechanism of neuronal death induced by exposure to these peptides. Peptides homologous to the fragment 106-126 of prion protein, an integral part of all abnormal prion protein isoforms that accumulate in the brain of patients with prion-related encephalopathies, are neurotoxic, fibrillogenic, and have a secondary structure largely composed of beta-sheet and proteinase-resistant properties.
在遗传学和生物化学研究的支持下，神经病理学观察表明β-淀粉样蛋白沉积在阿尔茨海默病发病机制中起核心作用。在朊病毒相关脑病中，异常形式的朊病毒蛋白也会形成淀粉样纤维并在大脑中积聚。在这两种情况下，淀粉样蛋白沉积都伴随着神经细胞丢失，但其发病机制和分子基础尚不清楚。与β-淀粉样蛋白及其片段以及朊病毒蛋白片段同源的合成肽分别用于研究脑沉积物形成机制以及这些蛋白质在阿尔茨海默病和朊病毒相关脑病中所起的作用。在实验条件下，β-淀粉样蛋白肽已被证明具有神经毒性和淀粉样变性，并且已经进行了大量研究以阐明暴露于这些肽所诱导的神经元死亡机制。与朊病毒蛋白片段106 - 126同源的肽是所有在朊病毒相关脑病患者大脑中积聚的异常朊病毒蛋白异构体的组成部分，具有神经毒性、纤维形成性，并且具有主要由β-折叠组成的二级结构和蛋白酶抗性。
