title: Synaptic dysfunction and disruption of postsynaptic drebrin-actin complex: a study of neurological disorders accompanied by cognitive deficits.
abstract: Many neurological disorders accompanied by cognitive deficits, including Alzheimer's disease (AD) and Down syndrome, exhibit abnormal dendritic spine morphology. Actin-based cytoskeletal network dynamics is critical for the regulation of spine morphology and function. Recent experimental data from an AD animal model revealed that defects in intracellular signaling cascades related to the accumulation of amyloid beta (Abeta) peptide cause disruption of the postsynaptic actin-regulatory machinery, including cofilin and drebrin. The level of postsynaptic drebrin, a major F-actin-binding protein in dendritic spines, correlates well with the severity of cognitive impairment. We propose that an imbalanced regulation of the actin-regulatory machinery (loss of drebrin and increase of dephosphorylated cofilin) results in synaptic dysfunction, which underlies the cognitive impairment accompanying neurological disorders and normal aging.
authors: Department of Neurobiology and Behavior, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
authors: Nobuhiko
authors: N
authors: Kojima
authors: Tomoaki
authors: T
authors: Shirao
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D001927:Brain Diseases / Q000473:pathology / Q000503:physiopathology* / Q000523:psychology; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D049229:Dendritic Spines / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000378:metabolism* / Q000473:pathology
chemical_list: D000199:Actins; D016229:Amyloid beta-Peptides; D009479:Neuropeptides; D017470:Receptors, Glutamate; C053386:drebrins