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2015 | 2 | 1 |

Article title

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


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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.







Physical description


13 - 5 - 2014
20 - 8 - 2015
26 - 11 - 2014


  • CNC
    – Center for Neuroscience and Cell Biology, University of Coimbra,
    Coimbra, Portugal
  • CNC
    – Center for Neuroscience and Cell Biology, University of Coimbra,
    Coimbra, Portugal
  • CNC
    – Center for Neuroscience and Cell Biology, University of Coimbra,
    Coimbra, Portugal
  • Faculty of
    Medicine, University of Coimbra, Coimbra, Portugal
  • Center for
    Neuroscience and Cell Biology, University of Coimbra, 3004-517
    Coimbra, Portugal
  • Faculty of
    Medicine, University of Coimbra, Coimbra, Portugal


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