Neurons and plaques of Alzheimer's disease patients highly express the neuronal membrane docking protein p42IP4/centaurin &agr;

The protein p42IP4 (also called centaurin &agr;), identified as a brain-specific InsP4/PtdInsP3 (PIP3)-binding protein, has been shown to be localized in human brain, specifically expressed in neurons. Several casein kinases have been found to be involved in Alzheimer's disease (AD) pathology. Since casein kinase I was reported to possess a binding domain for p42IP4, we here investigated the expression and localization of p42IP4 in AD brains. In cortical neurons of AD brains intracellular immunostaining for p42IP4 exceeded the level seen in these neurons of normal brain. Statistically, significantly more p42IP4-immunoreactive neurons were found in temporal and angular cortex of AD patients as compared to control brain. Mostly impressively, neuritic plaques displayed a very prominent signal. Thus, we suggest that the up-regulated p42IP4 in AD neurons may serve as a docking protein to recruit signaling molecules such as different subtypes of casein kinase I to the plasma membrane. This is the first indication for a functional interaction of these protein in possible neuronal damage. Therefore proteins such as p42IP4, central players in signaling, may be appropriate targets for preventing neurodegenerative processes.

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