Pregled bibliografske jedinice broj: 403313
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
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 // Biochimica et biophysica acta : molecular basis of disease, 1802 (2010), 7-8; 682-691 doi:10.1016/j.bbadis.2010.05.006 (međunarodna recenzija, članak, znanstveni)
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Naslov
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
Autori
Malnar, Martina ; Košiček, Marko ; Mitterreiter, Stefan ; Omerbašić, Damir ; Lichtenthaler, Stefan F. ; Goate, Alison ; Hećimović Katušić, Silva
Izvornik
Biochimica et biophysica acta : molecular basis of disease (0925-4439) 1802
(2010), 7-8;
682-691
Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni
Ključne riječi
Alzheimer’s disease ; amyloid-β ; APP ; cholesterol ; β-secretase ; NPC1
Sažetak
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.
Izvorni jezik
Engleski
Znanstvena područja
Biologija, Temeljne medicinske znanosti
POVEZANOST RADA
Projekti:
098-0982522-2525 - Mehanizam djelovanja kolesterola u nastanku Alzheimerove bolesti (Katušić Hećimović, Silva, MZOS ) ( CroRIS)
Ustanove:
Institut "Ruđer Bošković", Zagreb
Citiraj ovu publikaciju:
Časopis indeksira:
- Current Contents Connect (CCC)
- Web of Science Core Collection (WoSCC)
- Science Citation Index Expanded (SCI-EXP)
- SCI-EXP, SSCI i/ili A&HCI
- Scopus