This paper reports that a specific NMDA receptor activation in neurons leads to an increase of α-secretase-mediated APP processing. Interestingly, this effect is inhibited by chelating extracellular calcium with EGTA.
Our group has previously shown that an increase of intracellular calcium mediated by L-type voltage-dependent calcium channels has the opposite effect of decreasing the α-secretase pathway activity (1).
It would be interesting to investigate how the activation of the NMDA receptor can lead to an activation of the enzymes responsible for α-secretion, and what could account for an apparent contradictory effect of calcium influx, depending on the source of calcium that has been stimulated.
1. Pierrot N, Ghisdal P, Caumont AS, Octave JN. Intraneuronal amyloid-beta1-42 production triggered by sustained increase of cytosolic calcium concentration induces neuronal death. J Neurochem. 2004 Mar;88(5):1140-50. Abstract
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