Sorting Nexin 27 Regulates Aß Production through Modulating ?-Secretase Activity
Article Nov 06, 2014
Xin Wang, Timothy Huang, Yingjun Zhao, Qiuyang Zheng, Robert C. Thompson, Guojun Bu, Yun-wu Zhang, Wanjin Hong, Huaxi Xu
Summary: Patients with Down syndrome (DS) invariably develop Alzheimer’s disease (AD) pathology in their 40s. We have recently found that overexpression of a chromosome 21-encoded microRNA-155 results in decreased levels of the membrane trafficking component, SNX27, diminishing glutamate receptor recycling and thereby impairing synaptic functions in DS. Here, we report a function of SNX27 in regulating β-amyloid (Aβ) generation by modulating γ-secretase activity. Downregulation of SNX27 using RNAi increased Aβ production, whereas overexpression of full-length SNX27, but not SNX27ΔPDZ, reversed the RNAi-mediated Aβ elevation. Moreover, genetic deletion of Snx27 promoted Aβ production and neuronal loss, whereas overexpression of SNX27 using an adeno-associated viral (AAV) vector reduced hippocampal Aβ levels in a transgenic AD mouse model. SNX27 associates with the γ-secretase complex subunit presenilin 1; this interaction dissociates the γ-secretase complex, thus decreasing its proteolytic activity. Our study establishes a molecular mechanism for Aβ-dependent pathogenesis in both DS and AD.
Researchers have identified a mechanism by which brain-derived neurotrophic factor (BDNF) can suppress GABAergic transmission in hippocampus. In this article, Dr. Rajamani Selvam explains how he and his team achieved these results, and their potential impact on the treatment of neurological disease.READ MORE
A video showing the birth of an incredible network of neurons in the nervous system of a Zebrafish has won first prize at the Nikon Small World in Motion Awards, which highlight the best in photography and video captured through the microscope lens. We caught up with researchers behind the video to find out more.READ MORE