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  • Title: Presenilins are not required for A beta 42 production in the early secretory pathway.
    Author: Wilson CA, Doms RW, Zheng H, Lee VM.
    Journal: Nat Neurosci; 2002 Sep; 5(9):849-55. PubMed ID: 12145638.
    Abstract:
    Presenilins 1 and 2 (PS1/PS2) have been suggested to be gamma-secretases responsible for the proteolytic cleavage of amyloid precursor protein (APP) to form amyloid-beta (A beta), a protein implicated in the development of Alzheimer's disease. Here we examined whether these presenilins are required for the generation of multiple A beta species by analyzing the production of several forms of secreted and intracellular A beta in mouse cells lacking PS1, PS2 or both proteins. Although most A beta species were abolished in PS1/PS2(-/-) cells, the production of intracellular A beta 42 generated in the endoplasmic reticulum/intermediate compartment was unaffected by the absence of these proteins, either singly or in combination. These results indicate that production of this pool of A beta occurs independently of PS1/PS2, and therefore, another gamma-secretase activity must be responsible for cleavage of APP within the early secretory compartments.
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