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Pregled bibliografske jedinice broj: 892893

Regulatory effects of simvastatin and apoJ on APP processing and amyloid-beta clearance in blood-brain barrier endothelial cells


Zandl-Lang, Martina; Fanaee-Danesh, Elham; Sun, Yidan; Cancar, Igor; Gali, Chaitanya; Kober, Alexandra; Albrecher, Nicole; Tam-Amersdorfer, Caremen; Stracke, Anika; Storck, Steffen et al.
Regulatory effects of simvastatin and apoJ on APP processing and amyloid-beta clearance in blood-brain barrier endothelial cells // Biochimica and biophysica acta. Molecular and cell biology of lipids, 1863 (2017), 1; 40-60 doi:10.1016/j.bbalip.2017.09.008 (međunarodna recenzija, članak, znanstveni)


Naslov
Regulatory effects of simvastatin and apoJ on APP processing and amyloid-beta clearance in blood-brain barrier endothelial cells
(Regulatory effects of simvastatin and apoJ on APP processing and amyloid-β clearance in blood-brain barrier endothelial cells)

Autori
Zandl-Lang, Martina ; Fanaee-Danesh, Elham ; Sun, Yidan ; Cancar, Igor ; Gali, Chaitanya ; Kober, Alexandra ; Albrecher, Nicole ; Tam-Amersdorfer, Caremen ; Stracke, Anika ; Storck, Steffen ; Saeed, Ahmed ; Štefulj, Jasminka ; Pietrzik, Claus ; Wilson, Mark ; Bjoerkhem, Ingemar ; Panzenboeck, Ute

Izvornik
Biochimica and biophysica acta. Molecular and cell biology of lipids (1388-1981) 1863 (2017), 1; 40-60

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Blood-brain barrier ; amyloid-β ; cholesterol ; simvastatin ; clusterin/apoJ ; LRP1

Sažetak
Amyloid-β peptides (Aβ) accumulate in cerebral capillaries indicating a central role of the blood-brain barrier (BBB) in the pathogenesis of Alzheimer’s disease (AD). Although a relationship between apolipoprotein-, cholesterol- and Aβ metabolism is evident, the interconnecting mechanisms operating in brain capillary endothelial cells (BCEC) are poorly understood. ApoJ (clusterin) is present in HDL that regulates cholesterol metabolism which is disturbed in AD. ApoJ levels are increased in AD brains and in plasma of cerebral amyloid angiopathy (CAA) patients. ApoJ may bind, prevent fibrillization, and enhance clearance of Aβ. We here define a connection of apoJ and cellular cholesterol homeostasis in amyloid precursor protein (APP) processing/Aβ metabolism at the BBB. Silencing of apoJ in primary porcine (p)BCEC decreased intracellular APP and Aβ oligomer levels while the addition of purified apoJ to pBCEC increased intracellular APP and enhanced Aβ clearance across the pBCEC monolayer. Treatment of pBCEC with Aβ [1-40] increased expression of apoJ and receptors involved in amyloid transport including lipoprotein receptor-related protein 1 [LRP1]. In accordance, cerebromicrovascular endothelial cells isolated from 3xTg AD mice showed elevated expression levels of apoJ and LRP1 as compared to Non-Tg animals. Treatment of pBCEC with HMGCoA-reductase inhibitor simvastatin markedly increased intracellular and secreted apoJ levels, in parallel increased secreted Aβ oligomers and reduced Aβ uptake and cell-associated Aβ oligomers. Simvastatin effects on apoJ, APP processing, and LRP1 expression in BCEC were confirmed in the mouse model. We suggest a close and complex interaction of apoJ, cholesterol homeostasis, and APP/Aβ processing and clearance at the BBB.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti



POVEZANOST RADA


Ustanove
Institut "Ruđer Bošković", Zagreb

Autor s matičnim brojem:
Jasminka Štefulj, (232860)

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


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