Naslov
Increased formation of Aβ in CHO-NPC1 KO cells is not related to cholesterol levels solely

Autori
Malnar, Martina ; Goate, Alison ; Hećimović, Silva

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Book of Abstracts - 2nd Summer Course on Mass Spectrometry in Biotechnology and Medicine / Kirsch, Stephan - , 2007, 63-63

Skup
2nd Summer Course on Mass Spectrometry in Biotechnology and Medicine

Mjesto i datum
Dubrovnik, Hrvatska, 07.07.2007. - 14.07.2007

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
Alzheimer's disease; amyloid-beta; cholesterol; neurodegeneration

Sažetak
Cholesterol levels modulate formation of amyloid-β peptide (Aβ ) and pathogenesis of Alzheimer’ s disease (AD). Cholesterol accumulation in late endosomal/lysosomal compartments in lysosomal storage disorder Niemann Pick type C (NPC) leads to increased Aβ , like in AD. To elucidate the mechanism of increased Aβ formation upon NPC1 dysfunction, we monitored cholesterol-effect on APP processing between CHO-NPC1 KO and CHOwt cells. We found that cholesterol accumulation in CHO-NPC1 KO cells does not lead to increased formation of AICD, in contrast to Aβ . In vitro gamma-secretase assay and pulse chase assay confirmed that the effect on Aβ in NPC1 deficient cells is not due to altered gamma-secretase activity. Indeed, we observed 1.3 fold increased β -secretase activity in CHO-NPC1 KO vs. CHOwt cells. Intriguingly, in C99-transfected cells, in which Aβ formation is dependent on β -secretase activity only, we detected increased Aβ levels in CHO-NPC1 KO vs. CHOwt cells. In NPC1 KO cholesterol depletion lowered Aβ to the levels as in untreated wt cells, indicating that increased formation of Aβ in NPC disease is dependent on cholesterol levels. However, cholesterol loading in CHOwt cells did not raise the levels of Aβ as in CHO-NPC1 KO, suggesting that AD-like phenotype of Aβ upon NPC1 dysfunction may not be related to cholesterol levels solely.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA