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A(beta) peptides as one of the crucial volume transmission signals in the trophic units and their interactions with homocysteine. Physiological implications and relevance for Alzheimer's disease

机译:Aβ肽是营养单元中至关重要的体积传输信号之一,并且与高半胱氨酸相互作用。阿尔茨海默氏病的生理学意义和相关性

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摘要

Amyloid peptides (Ap) can operate as volume transmission (VT) signals since they are continuously released from cells of the central nervous system and diffuse in the extra-cellular space of the brain. They have both regulatory and trophic functions on cellular networks. In agreement with Ap regulatory actions on glial-neuronal networks, the present paper reports new findings demonstrating that intrastriatal injections of Ap peptides reduce striatal tyrosine hydroxylase, increase striatal GFAP immunoreactivities and lower pain threshold in experimental rats. Furthermore, it has been demonstrated that exogenous homocysteine (Hey) binds Ap(l-40) favouring its p-sheet conformation both in vitro and in vivo and hence the formation of p-fibrils and development of neurotoxicity.Thus, the hypothesis is discussed that Ap peptides represent crucial VT-signals in the brain and their action is altered by dysmetabolic signals such as high Hey extra-cellular levels, known to be an important risk factor for Alzheimer's disease.
机译:淀粉样蛋白肽(Ap)可以作为体积传输(VT)信号,因为它们从中枢神经系统的细胞中连续释放并扩散到大脑的细胞外空间。它们在蜂窝网络上既具有调节功能又具有营养功能。与Ap对神经胶质神经网络的调节作用相一致,本论文报道了新发现,表明纹状体内注射Ap肽可降低实验大鼠的纹状体酪氨酸羟化酶,增加纹状体GFAP免疫反应性并降低疼痛阈值。此外,已经证明外源性高半胱氨酸(Hey)结合Ap(l-40)有利于其在体内和体外的p-sheet构象,因此p-原纤维的形成和神经毒性的发展。因此,讨论了这一假说Ap肽代表大脑中至关重要的VT信号,并且其运动受到代谢异常信号(例如高Hey细胞外水平)的影响而改变,这被认为是阿尔茨海默氏病的重要危险因素。

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