Reduction of NR1 and phosphorylated Ca2+/calmodulin-dependent protein kinase II levels in Alzheimer's disease.

Abstract

Ca2+ influx through the N-methyl-D-aspartate-type glutamate receptor leads to activation and postsynaptic accumulation of Ca2+/calmodulin-dependent protein kinase II. NR1 and NR2B subunits of N-methyl-D-aspartate receptor serve as high-affinity Ca2+/calmodulin-dependent protein kinase II docking sites in dendritic spines on autophosphorylation of Ca2+/calmodulin-dependent protein kinase II. By comparative Western blot analysis, we show a reduction of NR1 and phosphorylated Ca2+/calmodulin-dependent protein kinase II levels in the frontal cortex and hippocampus of Alzheimer's disease brains. We also found a significant correlation between phosphorylated Ca2+/calmodulin-dependent protein kinase II and NR1 levels. Our study extends the view that N-methyl-D-aspartate receptor deficiency underlies memory impairment in Alzheimer's disease, and that this process likely involves insufficient activation of Ca2+/calmodulin-dependent protein kinase II.

• Authors: Naoki Amada, Koutoku Aihara, Rivka Ravid, Masato Horie
• Journal: Neuroreport (Neuroreport) Vol. 16 Issue 16 Pg. 1809-13 (Nov 07 2005) ISSN: 0959-4965 [Print] England
• PMID: 16237332 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Flavoproteins
• NDOR1 protein, human
• Oxidoreductases
• Calcium-Calmodulin-Dependent Protein Kinase Type 2
• Calcium-Calmodulin-Dependent Protein Kinases

Topics

• Aged
• Aged, 80 and over
• Alzheimer Disease (enzymology, metabolism)
• Blotting, Western (methods)
• Calcium-Calmodulin-Dependent Protein Kinase Type 2
• Calcium-Calmodulin-Dependent Protein Kinases (metabolism)
• Female
• Flavoproteins (metabolism)
• Gene Expression Regulation (physiology)
• Humans
• Male
• Middle Aged
• Oxidoreductases (metabolism)
• Phosphorylation
• Postmortem Changes