title: Partial Amelioration of Synaptic and Cognitive Deficits by Inhibiting Cofilin Dephosphorylation in an Animal Model of Alzheimer's Disease.
abstract: The loss of synaptic structure and function has been linked to the cognitive impairment of Alzheimer's disease (AD). Dysregulation of the actin cytoskeleton, which plays a key role in regulating the integrity of synapses and the transport of synaptic proteins, has been suggested to contribute to the pathology of AD. In this study, we found that glutamate receptor surface expression and synaptic function in frontal cortical neurons were significant diminished in a familial AD (FAD) model, which was correlated with the reduction of phosphorylated cofilin, a key protein regulating the dynamics of actin filaments. Injecting a cofilin dephosphorylation inhibitory peptide to FAD mice led to the partial rescue of the surface expression of AMPA and NMDA receptor subunits, as well as the partial restoration of AMPAR- and NMDAR-mediated synaptic currents. Moreover, the impaired working memory and novel object recognition memory in FAD mice were partially ameliorated by injections of the cofilin dephosphorylation inhibitory peptide. These results suggest that targeting the cofilin-actin signaling holds promise to mitigate the physiological and behavioral abnormality in AD.
authors.affiliation: Department of Physiology & Biophysics, State University of New York at Buffalo, Buffalo, NY, USA.|Department of Neurology & Institute of Neurology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yulei
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Physiology & Biophysics, State University of New York at Buffalo, Buffalo, NY, USA.|VA Western New York Healthcare System, Buffalo, NY, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Wei
authors.affiliation: Department of Physiology & Biophysics, State University of New York at Buffalo, Buffalo, NY, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Physiology & Biophysics, State University of New York at Buffalo, Buffalo, NY, USA.|VA Western New York Healthcare System, Buffalo, NY, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhong
authors.affiliation: Department of Physiology & Biophysics, State University of New York at Buffalo, Buffalo, NY, USA.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Xiong
authors.affiliation: Department of Physiology & Biophysics, State University of New York at Buffalo, Buffalo, NY, USA.
authors.forename: Aiyi
authors.initials: A
authors.lastname: Liu
authors.affiliation: Department of Physiology & Biophysics, State University of New York at Buffalo, Buffalo, NY, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Neurology & Institute of Neurology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Shengdi
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Physiology & Biophysics, State University of New York at Buffalo, Buffalo, NY, USA.|VA Western New York Healthcare System, Buffalo, NY, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yan
mesh_terms: D051339:Actin Depolymerizing Factors / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology* / Q000523:psychology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003072:Cognition Disorders / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D008568:Memory / Q000502:physiology*; D008822:Mice, Transgenic; D010766:Phosphorylation; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D017966:Pyramidal Cells / Q000378:metabolism / Q000473:pathology; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000378:metabolism* / Q000473:pathology*; D046509:Tissue Culture Techniques
chemical_list: C545487:APP protein, human; D051339:Actin Depolymerizing Factors; D000199:Actins; D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; D053764:Presenilin-1; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate
keywords: Actin; Alzheimer’s disease; cofilin; glutamate receptors; novel object recognition memory; prefrontal cortex; working memory