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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


Malnar, Martina; Košiček, Marko; Mitterreiter, Stefan; Omerbašić, Damir; Lichtenthaler, Stefan F.; Goate, Alison; Hećimović Katušić, Silva
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)


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


Projekt / tema
098-0982522-2525 - Mehanizam djelovanja kolesterola u nastanku Alzheimerove bolesti (Silva Hećimović, )

Ustanove
Institut "Ruđer Bošković", Zagreb

Citiraj ovu publikaciju

Malnar, Martina; Košiček, Marko; Mitterreiter, Stefan; Omerbašić, Damir; Lichtenthaler, Stefan F.; Goate, Alison; Hećimović Katušić, Silva
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)
Malnar, M., Košiček, M., Mitterreiter, S., Omerbašić, D., Lichtenthaler, S., Goate, A. & Hećimović Katušić, S. (2010) 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 (7-8), 682-691 doi:10.1016/j.bbadis.2010.05.006.
@article{article, year = {2010}, pages = {682-691}, DOI = {10.1016/j.bbadis.2010.05.006}, keywords = {Alzheimer’s disease, amyloid-β, APP, cholesterol, β-secretase, NPC1}, journal = {Biochimica et biophysica acta : molecular basis of disease}, doi = {10.1016/j.bbadis.2010.05.006}, volume = {1802}, number = {7-8}, issn = {0925-4439}, title = {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}, keyword = {Alzheimer’s disease, amyloid-β, APP, cholesterol, β-secretase, NPC1} }

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


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