. Toward structural elucidation of the gamma-secretase complex. Structure. 2009 Mar 11;17(3):326-34. PubMed.


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  1. The presenilin hypothesis should be explained taken into account the latest findings from the three-dimensional structure of secretase complex and the monomeric condition.

    If the water channels were, in fact, two distinct channels through which the same molecule of APP, in addition to water, could access the active site of the complex but suffering different strain, it probably will result in different products, as outlined in the model of progressive proteolysis of Ihara. This would agree with the monomeric condition.

    It is easy to reach this conclusion through mathematical kinetic equations.

    With this in mind presenilin would act on the APP as a high pass filter where probably Aβ42, in a suitable concentration range, were not a harmful substance but part (C49,...) of a modeling system of the brain.

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