Nalazite se na CroRIS probnoj okolini. Ovdje evidentirani podaci neće biti pohranjeni u Informacijskom sustavu znanosti RH. Ako je ovo greška, CroRIS produkcijskoj okolini moguće je pristupi putem poveznice www.croris.hr
izvor podataka: crosbi !

Enhanced proteolysis by the Alzheimer's protease BACE1 in NPC1 mouse brains is due to sequestration of its substrates within early endosomes (CROSBI ID 713656)

Prilog sa skupa u zborniku | sažetak izlaganja sa skupa

Rastija, Ana ; Meglaj, Sarah ; Tahirovic, Sabina ; Lichtenthaler, Stefan F. ; Hecimovic, Silva Enhanced proteolysis by the Alzheimer's protease BACE1 in NPC1 mouse brains is due to sequestration of its substrates within early endosomes. 2021. str. 157-157

Podaci o odgovornosti

Rastija, Ana ; Meglaj, Sarah ; Tahirovic, Sabina ; Lichtenthaler, Stefan F. ; Hecimovic, Silva

engleski

Enhanced proteolysis by the Alzheimer's protease BACE1 in NPC1 mouse brains is due to sequestration of its substrates within early endosomes

Niemann-Pick type C (NPC) is a rare inherited lysosomal storage disorder that shares several pathological features with Alzheimer's disease (AD), including dysfunction of the endolysosomal pathway and increased levels of amyloid-beta peptides (Aβ). The Aβ peptides are generated by the proteolytic cleavage of the β-amyloid precursor protein (APP) initiated by the β-site amyloid precursor protein cleavage enzyme 1 (BACE1). We have previously shown in NPC1-null cells and in NPC1-mouse brains an enhanced cleavage by BACE1 of APP, and also exclusive BACE1 substrates, seizure protein 6 (Sez6), and seizure 6-like protein (Sez6L). In this work, we tested the hypothesis that enhanced proteolysis by BACE1 in NPC disease brains is due to accumulation of BACE1 and its substrates within the endolysosomal pathway. We performed endosome fractionation of 10-weeks old cerebella from wild type (wt) and NPC1 mice using ultracentrifugation in discontinuous sucrose gradient. Fractions were collected and analyzed by western blotting. The levels of free cholesterol were determined using the Amplex Red Cholesterol Assay kit. We observed increased levels and different distribution of late and early endocytic markers in NPC1 vs. wt fractions. Also, Sez6 and especially Sez6L showed different distribution in NPC1 vs. wt mouse cerebella. We noticed increased free cholesterol levels in late vs. early endosome fractions in NPC1 mouse cerebella. These findings support that altered endocytic trafficking of BACE1 and its substrates, and their accumulation within early endosomes may likely cause increased proteolysis by BACE1 in NPC disease brains. Further studies are needed to elucidate the potential role of BACE1 in the pathogenesis of NPC disease.

Niemann-Pick type C disease ; NPC1 ; Amyloid-beta peptides ; Aβ ; BACE1

nije evidentirano

nije evidentirano

nije evidentirano

nije evidentirano

nije evidentirano

nije evidentirano

Podaci o prilogu

157-157.

2021.

objavljeno

Podaci o matičnoj publikaciji

Podaci o skupu

New Horizons in Alzheimer's Disease (Hybrid edition)

poster

27.10.2021-28.10.2021

Leuven, Belgija

Povezanost rada

Biologija, Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)