Astaxanthin exerts protective effects similar to bexarotene in Alzheimer's disease by modulating amyloid beta and cholesterol homeostasis in blood-brain barrier endothelial cells

Publication date: Available online 2 May 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Elham Fanaee-Danesh, Chaitanya Chakravarthi Gali, Jelena Tadic, Martina Zandl-Lang, Alexandra Kober, Vicente Roca Agujetas, Cristina de Dios, Carmen Tam-Amersdorfer, Anika Stracke, Nicole Maria Albrecher, Anil Paul Chirackal Manavalan, Marielies Reiter, Yidan Sun, Anna Colell, Frank Madeo, Ernst Malle, Ute PanzenboeckAbstractThe pathogenesis of Alzheimer's disease (AD) is characterized by overproduction, impaired clearance, and deposition of amyloid-β peptides (Aβ) and connected to cholesterol homeostasis. Since the blood-brain barrier (BBB) is involved in these processes, we investigated effects of the retinoid-X-receptor agonist, bexarotene (Bex), and the peroxisome proliferator-activated-receptor-α agonist and antioxidant, astaxanthin (Asx), on pathways of cellular cholesterol metabolism, amyloid precursor protein processing/Aβ production and transfer at the BBB in vitro using primary porcine brain capillary endothelial cells (pBCEC), and in 3xTg AD mice.Asx/Bex downregulated transcription/activity of amyloidogenic BACE1 and reduced Aβ oligomers and ~80 kDa intracellular 6E10-reactive APP/Aβ species, while upregulating non-amyloidogenic ADAM10 and soluble APPα production in pBCEC. Asx/Bex enhanced Aβ clearance to the apical/plasma compartment of the in vitro BBB model. Asx/Bex increased expression levels of ABCA1, LRP-1, and/or APOA-I. A...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research