Changes in signal transduction in Alzheimer’s disease
We studied the signal transduction system including the receptor and protein kinase C (PKC) in Alzheimer’s disease (AD) brains. We used 3H-TCP as a ligand for the NMDA receptor-ion channel complex. The total concentrations of 3H-TCP binding sites were significantly reduced in AD frontal cortex. 3H-TCP binding sites spared in AD brains retained the affinity for the ligand and the reactivity to NMDA, l-glutamate, and glycine. We utilized antibodies to assess the degree of involvement of different PKC isoforms in AD. The concentration of PKC (βII) was lower in AD particulate fractions and higher in AD cytosol fractions. Immunocytochemical studies revealed reduced numbers of anti-PKC (βII)-immunopositive neurons. Anti-PKC (α) faintly stained entire plaques and surrounding glial cells. Anti-PKC (βI) stained dystrophic plaque neurites. Anti-PKC (βII) stained the amyloid-containing portions of plaques. These results suggest an involvement of second messenger cascades in the pathogenesis of AD in addition to neurotransmitters and their receptors.
KeywordsNMDA Receptor Neuritic Plaque Excitatory Amino Acid Receptor Phosphorylate Amyloid Precursor Protein Entire Plaque
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