PrNP‐induced effect over NMDA expression and signalling

Background Etiology of Alzheimer's disease (AD) remain unclear. Different pathological processes have been described, such as phosphorylation of tau protein, amyloid plaques, oxidative stress or neuroinflammation. It has been described that over‐activation of the NMDA receptor due to an increas...

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Bibliographic Details
Published in:Alzheimer's & dementia 2021-12, Vol.17, p.e053486-n/a
Main Authors: Brugal, Gemma Navarro, Rivas‐Santisteban, Rafael, Reyes, Irene, Marquez, Alejandro Lillo, Raïch, Iu, Franco, Rafael
Format: Article
Language:English
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Summary:Background Etiology of Alzheimer's disease (AD) remain unclear. Different pathological processes have been described, such as phosphorylation of tau protein, amyloid plaques, oxidative stress or neuroinflammation. It has been described that over‐activation of the NMDA receptor due to an increase in glutamate levels induces excitotoxicity in neurodegenerative disorders, on the other hand, these disorders course with a chronic neuroinflammation where PrNP prion protein could play an important role. Methods We have also analyzed NMDA induced neuronal activity using Fluo4AM and MEAs for real time measurement of calcium‐fluorescence. Different signaling pathways have been analyzed, such as MAPK phosphorylation (determined using AlphaScreen®SureFire® kit (Perkin Elmer) or Dynamic Mass Redistribution (analyzed by label‐free‐DMR technology). Results We have observed that the expression of PrNP protein in cortical and hippocampal primary cultures of microglial cells showed an important decrease in NMDA induced signaling. Moreover, expression of PrNP protein in cortical and hippocampal primary cultures of neuronal cells showed an important decrease in NMDA induced signaling. Finally, it has been observed that NMDA receptor functionality in the presence or in the absence of Tau protein (phosphorylated or not) and PrNP negatively affects NMDA induced activation of calcium release in neuronal primary cultures. Conclusion NMDA receptor activation is negatively affected by the presence of PrNP prion protein by decreasing the receptor expression levels and the induced function.
ISSN:1552-5260
1552-5279
DOI:10.1002/alz.053486