Selective filtering defect at the axon initial segment in Alzheimer’s disease mouse models

• DOI: 10.1073/pnas.1411837111
• Publication Date: 2014-09-18T03:33:28Z
• Authors: Xiaqin Sun; Yu Wu; Mingxue Gu; Zhuo Liu; Yuanlin Ma; Jun Li; Yan Zhang
• Keywords: Ankyrin

Axon pathology has been widely reported in Alzheimer's disease (AD) patients and AD mouse models. Herein we report that increased miR-342-5p down-regulates the expression of ankyrin G (AnkG), a protein known to play critical role establishing selective filtering machinery at axon initial segment (AIS). Diminished AnkG leads defective AIS cultured hippocampal neurons from models, as monitored by exclusion large macromolecules axons. Furthermore, AnkG-deficiency impairs localization Nav 1.6 channels confines NR2B somatodendritic compartments. The exogenous improved cognitive performance 12-mo-old APP/PS1 mice; thus, our data suggest impairment may important roles pathology.