Niemann Pick type C cells show cholesterol dependent decrease of APP expression at the cell surface and its increased processing through the β-secretase pathway (CROSBI ID 151618)
Prilog u časopisu | izvorni znanstveni rad | međunarodna recenzija
Podaci o odgovornosti
Malnar, Martina ; Košiček, Marko ; Mitterreiter, Stefan ; Omerbašić, Damir ; Lichtenthaler, Stefan F. ; Goate, Alison ; Hećimović Katušić, Silva
engleski
Niemann Pick type C cells show cholesterol dependent decrease of APP expression at the cell surface and its increased processing through the β-secretase pathway
The link between cholesterol and Alzheimer’s disease has recently been revealed in Niemann Pick type C disease. We found that NPC1-/- cells show decreased expression of APP at the cell surface and increased processing of APP through the β-secretase pathway resulting in increased C99, sAPPβ and intracellular Aβ40 levels. This effect is dependent on increased cholesterol levels, since cholesterol depletion reversed cell surface APP expression and lowered Aβ/C99 levels in NPC1-/- cells to the levels observed in wt cells. Finding that overexpression of C99, a direct gamma-secretase substrate, does not lead to increased intracellular Aβ levels in NPC1-/- cells vs. CHOwt suggests that the effect on intracellular Aβ upon cholesterol accumulation in NPC1-/- cells is not due to increased APP cleavage by gamma-secretase. Our results indicate that cholesterol may modulate APP processing indirectly by modulating APP expression at the cell surface and, thus, its cleavage by β-secretase.
Alzheimer’s disease ; amyloid-β ; APP ; cholesterol ; β-secretase ; NPC1
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nije evidentirano
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nije evidentirano
nije evidentirano
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Podaci o izdanju
1802 (7-8)
2010.
682-691
objavljeno
0925-4439
10.1016/j.bbadis.2010.05.006
Povezanost rada
Biologija, Temeljne medicinske znanosti