Curcumin Derivative GT863 Inhibits Amyloid-Beta Production via Inhibition of Protein N-Glycosylation.
Alkaloids
/ pharmacology
Amyloid Precursor Protein Secretases
/ metabolism
Amyloid beta-Peptides
/ biosynthesis
Animals
CHO Cells
Cricetulus
Curcumin
/ analogs & derivatives
Glycosylation
Humans
Mannosidases
/ metabolism
Membrane Glycoproteins
/ metabolism
Receptors, Notch
/ metabolism
Substrate Specificity
Swainsonine
/ pharmacology
Alzheimer’s disease
amyloid-β peptides
curcumin derivatives
glycosylation
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
03 02 2020
03 02 2020
Historique:
received:
27
12
2019
revised:
29
01
2020
accepted:
31
01
2020
entrez:
8
2
2020
pubmed:
8
2
2020
medline:
13
2
2021
Statut:
epublish
Résumé
Amyloid-β (Aβ) peptides play a crucial role in the pathogenesis of Alzheimer's disease (AD). Aβ production, aggregation, and clearance are thought to be important therapeutic targets for AD. Curcumin has been known to have an anti-amyloidogenic effect on AD. In the present study, we performed screening analysis using a curcumin derivative library with the aim of finding derivatives effective in suppressing Aβ production with improved bioavailability of curcumin using CHO cells that stably express human amyloid-β precursor protein and using human neuroblastoma SH-SY5Y cells. We found that the curcumin derivative GT863/PE859, which has been shown to have an inhibitory effect on Aβ and tau aggregation in vivo, was more effective than curcumin itself in reducing Aβ secretion. We further found that GT863 inhibited neither β- nor γ-secretase activity, but did suppress γ-secretase-mediated cleavage in a substrate-dependent manner. We further found that GT863 suppressed
Identifiants
pubmed: 32028683
pii: cells9020349
doi: 10.3390/cells9020349
pmc: PMC7072163
pii:
doi:
Substances chimiques
Alkaloids
0
Amyloid beta-Peptides
0
Membrane Glycoproteins
0
Receptors, Notch
0
nicastrin protein
0
kifunensine
0NI8960271
Mannosidases
EC 3.2.1.-
Amyloid Precursor Protein Secretases
EC 3.4.-
Curcumin
IT942ZTH98
Swainsonine
RSY4RK37KQ
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Déclaration de conflit d'intérêts
H.S. is President of Green Tech Co., Ltd. Other authors declare no conflict of interest.
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