The role of proteotoxic stress in vascular dysfunction in the pathogenesis of Alzheimer’s disease

Abstract: Alzheimer’s disease (AD) is the principal cause of dementia in the elderly; however, its prevalence is increasing due to the fact that current pharmaceuticals used to manage the symptoms are not capable of preventing, halting, or reversing disease progression. In the last decade, evidence has accumulated to support the hypothesis that a primary cerebral vascular dysfunction initiates the cascade of events that leads to neuronal injury and the subsequent cognitive decline observed in AD. The mechanisms underlying these vascular defects and their relationship with neurodegeneration are still poorly understood however. It is pathologically known that cerebrovascular dysfunctions can induce the deposition of amyloid-β (Aβ), an amyloidogenic and toxic peptide that in turn causes cerebrovascular degeneration. Mammalian cells regulate proteostasis and the functioning of intracellular organelles through diverse mechanisms such as the Unfolded Protein Response, the Ubiquitin-Proteasome System and autophagy; however, when these mechanisms cannot compensate for perturbations in homeostasis, the cell undergoes programmed death via apoptosis. This review summarizes recent studies that together correlate the deregulation of protein quality control pathways with dysfunction of vascular endothelial cells of the brain in AD, thus supporting the hypothesis that it is the vicious, progressive failure of the proteostatic network and endothelial activation that underlies the cerebrovascular changes that symptomize AD.

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch

Verweise und Beziehungen

• Erschienen in: The role of proteotoxic stress in vascular dysfunction in the pathogenesis of Alzheimer’s disease ; volume:2 ; number:1 ; year:2015 ; pages:67-81 ; extent:15 ; Endoplasmic reticulum stress in diseases ; 2, Heft 1 (2015), 67-81 (gesamt 15)

Beteiligte, Orts- und Zeitangaben

• Urheber: Fonseca, Ana Catarina R.G. ; Resende, Rosa ; Cardoso, Sandra M. ; Pereira, Cláudia F.

Weitere Informationen

• DOI: 10.1515/ersc-2015-0005
• URN: urn:nbn:de:101:1-2412171144287.082029761966
• Rechteinformation: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 15.08.2025, 07:25 MESZ