Sökning: onr:"swepub:oai:lup.lub.lu.se:9ff5eb78-f507-4513-97a6-60f65f7ce73e" >
ADAM10 and BACE1 ar...
-
Lundgren, Jolanta LKarolinska Institutet
(författare)
ADAM10 and BACE1 are localized to synaptic vesicles.
- Artikel/kapitelEngelska2015
Förlag, utgivningsår, omfång ...
Nummerbeteckningar
-
LIBRIS-ID:oai:lup.lub.lu.se:9ff5eb78-f507-4513-97a6-60f65f7ce73e
-
https://lup.lub.lu.se/record/7840316URI
-
https://doi.org/10.1111/jnc.13287DOI
-
http://kipublications.ki.se/Default.aspx?queryparsed=id:132257920URI
Kompletterande språkuppgifter
-
Språk:engelska
-
Sammanfattning på:engelska
Ingår i deldatabas
Klassifikation
-
Ämneskategori:art swepub-publicationtype
-
Ämneskategori:ref swepub-contenttype
Anmärkningar
-
Synaptic degeneration and accumulation of the neurotoxic amyloid β-peptide (Aβ) in the brain are hallmarks of Alzheimer disease. Aβ is produced by sequential cleavage of its precursor protein, APP, by the β-secretase BACE1 and γ-secretase. However, Aβ generation is precluded if APP is cleaved by the α-secretase ADAM10 instead of BACE1. We have previously shown that Aβ can be produced locally at the synapse. To study the synaptic localization of the APP processing enzymes we used western blotting to demonstrate that, compared to total brain homogenate, ADAM10 and BACE1 were greatly enriched in synaptic vesicles isolated from rat brain using controlled-pore glass chromatography, whereas Presenilin1 was the only enriched component of the γ-secretase complex. Moreover, we detected ADAM10 activity in synaptic vesicles and enrichment of the intermediate APP-C-terminal fractions (APP-CTFs). We confirmed the western blotting findings using in situ proximity ligation assay to demonstrate close proximity of ADAM10 and BACE1 with the synaptic vesicle marker synaptophysin in intact mouse primary hippocampal neurons. In contrast, only sparse co-localization of active γ-secretase and synaptophysin was detected. These results indicate that the first step of APP processing occurs in synaptic vesicles whereas the final step is more likely to take place elsewhere. This article is protected by copyright. All rights reserved.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
-
Ahmed, Saheeb
(författare)
-
Schedin-Weiss, SophiaKarolinska Institutet
(författare)
-
Gouras, GunnarLund University,Lunds universitet,Experimentell demensforskning,Forskargrupper vid Lunds universitet,Experimental Dementia Research,Lund University Research Groups(Swepub:lu)med-grg
(författare)
-
Winblad, BengtKarolinska Institutet
(författare)
-
Tjernberg, Lars OKarolinska Institutet
(författare)
-
Frykman, SusanneKarolinska Institutet
(författare)
-
Karolinska InstitutetExperimentell demensforskning
(creator_code:org_t)
Sammanhörande titlar
-
Ingår i:Journal of Neurochemistry: Wiley135:3, s. 606-6151471-41590022-3042
Internetlänk
Hitta via bibliotek
Till lärosätets databas