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Partial Amelioration of Synaptic and Cognitive Deficits by Inhibiting Cofilin Dephosphorylation in an Animal Model of Alzheimer's Disease.
- Source :
- Journal of Alzheimer's Disease; 2016, Vol. 53 Issue 4, p1419-1432, 14p
- Publication Year :
- 2016
-
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. [ABSTRACT FROM AUTHOR]
- Subjects :
- ALZHEIMER'S disease
CYTOSKELETON
GLUTAMATE receptors
NEURONS
DEPHOSPHORYLATION
MEMORY
BIOLOGICAL transport
MUSCLE protein metabolism
ANIMAL experimentation
BIOLOGICAL models
CELL culture
CELL receptors
COGNITION disorders
FRONTAL lobe
RESEARCH methodology
MEMBRANE proteins
MICE
MICROFILAMENT proteins
NERVOUS system
PHOSPHORYLATION
PROTEIN precursors
RATS
TISSUE culture
PHYSIOLOGY
PSYCHOLOGY
Subjects
Details
- Language :
- English
- ISSN :
- 13872877
- Volume :
- 53
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- Journal of Alzheimer's Disease
- Publication Type :
- Academic Journal
- Accession number :
- 117365415
- Full Text :
- https://doi.org/10.3233/JAD-160167