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: Nobuhiko Kojima, Tomoaki Shirao
• Journal: Neuroscience research (Neurosci Res) Vol. 58 Issue 1 Pg. 1-5 (May 2007) ISSN: 0168-0102 [Print] Ireland
• PMID: 17379343 (Publication Type: Journal Article, Review)

Chemical References

• Actins
• Amyloid beta-Peptides
• Neuropeptides
• Receptors, Glutamate
• drebrins

Topics

• Actins (genetics, metabolism)
• Amyloid beta-Peptides (metabolism)
• Animals
• Brain (metabolism, pathology, physiopathology)
• Brain Diseases (pathology, physiopathology, psychology)
• Cognition Disorders (etiology, pathology, physiopathology)
• Dendritic Spines (metabolism, pathology)
• Humans
• Neuropeptides (genetics, metabolism)
• Receptors, Glutamate (genetics, metabolism)
• Synapses (metabolism, pathology)