Oxidative stress triggers the amyloidogenic pathway in human vascular smooth muscle cells
M Coma, FX Guix, G Ill-Raga, I Uribesalgo… - Neurobiology of …, 2008 - Elsevier
Neurobiology of aging, 2008•Elsevier
Cerebral amyloid angiopathy, associated to most cases of Alzheimer's disease (AD), is
characterized by the deposition of amyloid ß-peptide (Aß) in brain vessels, although the
origin of the vascular amyloid deposits is still controversial: neuronal versus vascular. In the
present work, we demonstrate that primary cultures of human cerebral vascular smooth
muscle cells (HC-VSMCs) have all the secretases involved in amyloid ß-protein precursor
(APP) cleavage and produce Aß1–40 and Aß1–42. Oxidative stress, a key factor in the …
characterized by the deposition of amyloid ß-peptide (Aß) in brain vessels, although the
origin of the vascular amyloid deposits is still controversial: neuronal versus vascular. In the
present work, we demonstrate that primary cultures of human cerebral vascular smooth
muscle cells (HC-VSMCs) have all the secretases involved in amyloid ß-protein precursor
(APP) cleavage and produce Aß1–40 and Aß1–42. Oxidative stress, a key factor in the …
Cerebral amyloid angiopathy, associated to most cases of Alzheimer's disease (AD), is characterized by the deposition of amyloid ß-peptide (Aß) in brain vessels, although the origin of the vascular amyloid deposits is still controversial: neuronal versus vascular. In the present work, we demonstrate that primary cultures of human cerebral vascular smooth muscle cells (HC-VSMCs) have all the secretases involved in amyloid ß-protein precursor (APP) cleavage and produce Aß1–40 and Aß1–42. Oxidative stress, a key factor in the etiology and pathophysiology of AD, up-regulates ß-site APP cleaving enzyme 1 (BACE1) expression, as well as Aß1–40 and Aß1–42 secretion in HC-VSMCs. This process is mediated by c-Jun N-terminal Kinase and p38 MAPK signaling and appears restricted to BACE1 regulation as no changes in the other secretases were observed. In conclusion, oxidative stress-mediated up-regulation of the amyloidogenic pathway in human cerebral vascular smooth muscle cells may contribute to the overall cerebrovascular amyloid angiopathy observed in AD patients.
Elsevier