Institute of Neuroscience, CNR-Pisa, 56100 Pisa, Italy.
Expert Rev Neurother. 2009 Nov;9(11):1635-45. doi: 10.1586/ern.09.107.
Genetic and biological studies provide strong support for the hypothesis that accumulation of beta amyloid peptide (Abeta) contributes to the etiology of Alzheimer's disease (AD). Growing evidence indicates that oligomeric soluble Abeta plays an important role in the development of synaptic dysfunction and the impairment of cognitive function in AD. The receptor for advanced glycation end products (RAGE), a multiligand receptor in the immunoglobulin superfamily, acts as a cell surface binding site for Abeta and mediates alternations in the phosphorylation state of mitogen-activated protein kinase (MAPKs). Recent results have shown that MAPKs are involved in neurodegenerative processes. In particular, changes in the phosphorylation state of various MAPKs by Abeta lead to synaptic dysfunction and cognitive decline, as well as development of inflammatory responses in AD. The present review summarizes the evidence justifying a novel therapeutic approach focused on inhibition of RAGE signaling in order to arrest or halt the development of neuronal dysfunction in AD.
遗传和生物学研究为β淀粉样肽（Abeta）积累导致阿尔茨海默病（AD）的假说提供了强有力的支持。越来越多的证据表明，寡聚可溶性 Abeta 在突触功能障碍的发展和 AD 认知功能的损害中发挥重要作用。晚期糖基化终产物受体（RAGE）是免疫球蛋白超家族中的多配体受体，作为 Abeta 的细胞表面结合位点，介导丝裂原活化蛋白激酶（MAPKs）的磷酸化状态的改变。最近的结果表明，MAPKs 参与神经退行性过程。特别是，Abeta 对各种 MAPKs 磷酸化状态的改变导致突触功能障碍和认知能力下降，以及 AD 中炎症反应的发展。本综述总结了支持一种新的治疗方法的证据，该方法侧重于抑制 RAGE 信号，以阻止或停止 AD 中神经元功能障碍的发展。
