Department of Anatomy, Medical College of Jinan University, Guangzhou 510630, China.
Department of Neurology, Guangzhou Red Cross Hospital, Medical College, Jinan University, Guangzhou 510220, China.
Neural Plast. 2017;2017:8197085. doi: 10.1155/2017/8197085. Epub 2017 Jul 5.
Amyloid- (A) plays an important role in Alzheimer's disease (AD), as oligomeric A induces loss of postsynaptic AMPA receptors (AMPARs) leading to cognitive deficits. The loss of postsynaptic AMPARs is mediated through the clathrin-dependent endocytosis pathway, in which endophilin2 is one of the important regulatory proteins. Endophilin2, which is enriched in both the pre- and postsynaptic membrane, has previously been reported to be important for recycling of synaptic vesicles at the presynaptic membrane. However, the role of endophilin2 in oligomeric A-induced postsynaptic AMPAR endocytosis is not well understood. In this study, we show that endophilin2 does not affect constitutive AMPAR endocytosis. Endophilin2 knockdown, but not overexpression, resisted oligomeric A-induced AMPAR dysfunction. Moreover, endophilin2 colocalized and interacted with GluA1, a subunit of AMPAR, to regulate oligomeric A-induced AMPAR endocytosis. Thus, we have determined a role of endophilin2 in oligomeric A-induced postsynaptic AMPAR dysfunction, indicating possible directions for preventing the loss of AMPARs in cognitive impairment and providing evidence for the clinical treatment of AD.
淀粉样蛋白（A）在阿尔茨海默病（AD）中发挥着重要作用，因为寡聚 A 诱导突触后 AMPA 受体（AMPAR）丧失，导致认知缺陷。突触后 AMPAR 的丧失是通过网格蛋白依赖性内吞作用途径介导的，其中内收蛋白 2 是重要的调节蛋白之一。内收蛋白 2 在突触前和突触后膜中均丰富，先前已被报道对于突触小泡在突触前膜的再循环很重要。然而，内收蛋白 2 在寡聚 A 诱导的突触后 AMPAR 内吞作用中的作用尚不清楚。在这项研究中，我们表明内收蛋白 2 不会影响组成型 AMPAR 内吞作用。内收蛋白 2 敲低，但不是过表达，抵抗寡聚 A 诱导的 AMPAR 功能障碍。此外，内收蛋白 2 与 AMPAR 的亚基 GluA1 共定位并相互作用，以调节寡聚 A 诱导的 AMPAR 内吞作用。因此，我们确定了内收蛋白 2 在寡聚 A 诱导的突触后 AMPAR 功能障碍中的作用，这表明了在认知障碍中防止 AMPAR 丧失的可能方向，并为 AD 的临床治疗提供了证据。
