Astaxanthin enhances autophagy, amyloid beta clearance and exerts anti-inflammatory effects in in vitro models of Alzheimer's disease-related blood brain barrier dysfunction and inflammation.
Mice
Animals
Swine
Alzheimer Disease
/ metabolism
Blood-Brain Barrier
/ metabolism
Amyloid beta-Peptides
/ metabolism
Endothelial Cells
/ metabolism
Amyloid beta-Protein Precursor
/ metabolism
Inflammation
/ drug therapy
Autophagy
Anti-Inflammatory Agents
/ pharmacology
Mice, Transgenic
Disease Models, Animal
Amyloid beta
Astaxanthin
Autophagy
Blood-brain barrier
Inflammation
Journal
Brain research
ISSN: 1872-6240
Titre abrégé: Brain Res
Pays: Netherlands
ID NLM: 0045503
Informations de publication
Date de publication:
15 11 2023
15 11 2023
Historique:
received:
31
05
2023
revised:
22
07
2023
accepted:
02
08
2023
medline:
23
10
2023
pubmed:
15
8
2023
entrez:
14
8
2023
Statut:
ppublish
Résumé
Defective degradation and clearance of amyloid-β as well as inflammation per se are crucial players in the pathology of Alzheimer's disease (AD). A defective transport across the blood-brain barrier is causative for amyloid-β (Aβ) accumulation in the brain, provoking amyloid plaque formation. Using primary porcine brain capillary endothelial cells and murine organotypic hippocampal slice cultures as in vitro models of AD, we investigated the effects of the antioxidant astaxanthin (ASX) on Aβ clearance and neuroinflammation. We report that ASX enhanced the clearance of misfolded proteins in primary porcine brain capillary endothelial cells by inducing autophagy and altered the Aβ processing pathway. We observed a reduction in the expression levels of intracellular and secreted amyloid precursor protein/Aβ accompanied by an increase in ABC transporters ABCA1, ABCG1 as well as low density lipoprotein receptor-related protein 1 mRNA levels. Furthermore, ASX treatment increased autophagic flux as evidenced by increased lipidation of LC3B-II as well as reduced protein expression of phosphorylated S6 ribosomal protein and mTOR. In LPS-stimulated brain slices, ASX exerted anti-inflammatory effects by reducing the secretion of inflammatory cytokines while shifting microglia polarization from M1 to M2 phenotype. Our data suggest ASX as potential therapeutic compound ameliorating AD-related blood brain barrier impairment and inflammation.
Identifiants
pubmed: 37579986
pii: S0006-8993(23)00289-5
doi: 10.1016/j.brainres.2023.148518
pii:
doi:
Substances chimiques
Amyloid beta-Peptides
0
astaxanthine
8XPW32PR7I
Amyloid beta-Protein Precursor
0
Anti-Inflammatory Agents
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
148518Informations de copyright
Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: I.I., D.L., T.L., I.S., S.F., M.P. and B.H.P. are presently or formerly affiliated with QPS Austria..