title: Selective filtering defect at the axon initial segment in Alzheimer's disease mouse models.
abstract: 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 a critical role in establishing selective filtering machinery at the axon initial segment (AIS). Diminished AnkG expression leads to defective AIS filtering in cultured hippocampal neurons from AD mouse models, as monitored by selective exclusion of large macromolecules from the axons. Furthermore, AnkG-deficiency impairs AIS localization of Nav 1.6 channels and confines NR2B to the somatodendritic compartments. The expression of exogenous AnkG improved the cognitive performance of 12-mo-old APP/PS1 mice; thus, our data suggest that AnkG and impairment of AIS filtering may play important roles in AD pathology.
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, College of Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China; and.
authors.forename: Xiaqin
authors.initials: X
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, College of Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China; and.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, College of Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China; and.
authors.forename: Mingxue
authors.initials: M
authors.lastname: Gu
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, College of Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China; and.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Peking University Sixth Hospital, Beijing 100191, China.
authors.forename: Yuanlin
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Peking University Sixth Hospital, Beijing 100191, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, College of Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China; and yanzhang@pku.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000502:physiology; D000818:Animals; D017487:Ankyrins / Q000235:genetics / Q000502:physiology; D001369:Axons / Q000473:pathology / Q000502:physiology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015536:Down-Regulation; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D050505:Mutant Proteins / Q000235:genetics / Q000502:physiology; D053764:Presenilin-1 / Q000235:genetics / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; C094681:Ank3 protein, mouse; D017487:Ankyrins; D035683:MicroRNAs; C581863:Mirn342 microRNA, mouse; D050505:Mutant Proteins; C121001:NR2B NMDA receptor; C508853:PSEN1 protein, human; D053764:Presenilin-1; D016194:Receptors, N-Methyl-D-Aspartate