Reduction of NR1 and phosphorylated Ca2+/calmodulin-dependent protein kinase II levels in Alzheimer's disease.
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.
Amada
Naoki
N
Second Institute of New Drug Discovery, Otsuka Pharmaceutical Co. Ltd, 463-10 Kagasuno, Kawauchi-cho, Tokushima, Japan.
Aihara
Koutoku
K
Ravid
Rivka
R
Horie
Masato
M
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology / Q000378:metabolism*; D015153:Blotting, Western / Q000379:methods; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D005260:Female; D005420:Flavoproteins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010088:Oxidoreductases / Q000378:metabolism*; D010766:Phosphorylation; D011180:Postmortem Changes
D005420:Flavoproteins; C478386:NDOR1 protein, human; D010088:Oxidoreductases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases