Asparagine endopeptidase cleaves tau at N167 after uptake into microglia.
AEP
Alzheimer's disease
Microglia
Proteolysis
Tau
Journal
Neurobiology of disease
ISSN: 1095-953X
Titre abrégé: Neurobiol Dis
Pays: United States
ID NLM: 9500169
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
22
03
2019
revised:
08
06
2019
accepted:
19
06
2019
pubmed:
24
6
2019
medline:
25
3
2020
entrez:
24
6
2019
Statut:
ppublish
Résumé
Tau cleavage by different proteolytic enzymes generates short, aggregation-prone fragments that have been implicated in the pathogenesis of Alzheimer's disease (AD). Asparagine endopeptidase (AEP) activity in particular has been associated with tau dysfunction and aggregation, and the activity of the protease is increased in both aging and AD. Using a mass spectrometry approach, we identified a novel tau cleavage site at N167 and confirmed its processing by AEP. In combination with the previously known site at N368, we show that AEP cleavage yields a tau fragment that is present in both control and AD brains at similar levels. AEP is a lysosomal enzyme, and our data suggest that it is expressed in microglia rather than in neurons. Accordingly, we observe tau cleavage at N167 and N368 after endocytotic uptake into microglia, but not neurons. However, tau
Identifiants
pubmed: 31229689
pii: S0969-9961(19)30176-7
doi: 10.1016/j.nbd.2019.104518
pii:
doi:
Substances chimiques
tau Proteins
0
Cysteine Endopeptidases
EC 3.4.22.-
asparaginylendopeptidase
EC 3.4.22.34
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
104518Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.