Melchor Jerry P, Pawlak Robert, Chen Zulin, Strickland Sidney
The Laboratory of Neurobiology and Genetics, The Rockefeller University, New York, NY 10021, USA.
J Mol Neurosci. 2003;20(3):287-9. doi: 10.1385/JMN:20:3:287.
Alzheimer's disease (AD) is the leading cause of cognitive decline in aged individuals. The pathological hallmarks of AD include the formation of neurofibrillary tangles, along with senile plaques that are mainly composed of the amyloid-beta (Abeta) peptide. Several lines of evidence implicate the tPA/plasmin system in AD. One type of cell death observed in AD is excitotoxic neuronal damage, and the tPA/plasmin system participates in excitotoxic cell death. Recent in vitro experiments report that the addition of aggregated Abeta peptide to primary cortical neurons leads to the up-regulation of tPA mRNA expression. Additionally, plasmin (activated by tPA) attenuates Abeta neurotoxicity by degrading the peptide and rendering it inactive. However, there is no evidence to demonstrate an in vivo contribution of the tPA/plasmin system in AD. We are currently examining the effects of the tPA/plasmin system on the deposition and toxicity of the Abeta peptide with in vivo paradigms of AD. We hope to define the contribution of the tPA/plasmin system in the development of AD pathology.
阿尔茨海默病（AD）是老年人认知衰退的主要原因。AD的病理特征包括神经原纤维缠结的形成，以及主要由β淀粉样蛋白（Aβ）肽组成的老年斑。多条证据表明组织型纤溶酶原激活物（tPA）/纤溶酶系统与AD有关。在AD中观察到的一种细胞死亡类型是兴奋性毒性神经元损伤，tPA/纤溶酶系统参与兴奋性毒性细胞死亡。最近的体外实验报告称，向原代皮层神经元中添加聚集的Aβ肽会导致tPA mRNA表达上调。此外，（由tPA激活的）纤溶酶通过降解该肽并使其失活来减轻Aβ神经毒性。然而，没有证据表明tPA/纤溶酶系统在AD中有体内作用。我们目前正在利用AD的体内模型研究tPA/纤溶酶系统对Aβ肽沉积和毒性的影响。我们希望确定tPA/纤溶酶系统在AD病理发展中的作用。
