. Synaptic NMDA receptor activation stimulates alpha-secretase amyloid precursor protein processing and inhibits amyloid-beta production. J Neurosci. 2009 Apr 8;29(14):4442-60. PubMed.

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  1. 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.

    References:

    . Intraneuronal amyloid-beta1-42 production triggered by sustained increase of cytosolic calcium concentration induces neuronal death. J Neurochem. 2004 Mar;88(5):1140-50. PubMed.