ER stress induced immunopathology involving complement in CADASIL: implications for therapeutics.
CADASIL
Complement
Interleukin 6
Intracellular adhesion molecule
Stroke
Vascular smooth muscle cells
Journal
Acta neuropathologica communications
ISSN: 2051-5960
Titre abrégé: Acta Neuropathol Commun
Pays: England
ID NLM: 101610673
Informations de publication
Date de publication:
08 05 2023
08 05 2023
Historique:
received:
30
12
2022
accepted:
26
03
2023
medline:
11
5
2023
pubmed:
9
5
2023
entrez:
9
5
2023
Statut:
epublish
Résumé
Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by NOTCH3 mutations. Typical CADASIL is characterised by subcortical ischemic strokes due to severe arteriopathy and fibrotic thickening of small arteries. Arteriolar vascular smooth muscle cells (VSMCs) are the key target in CADASIL, but the potential mechanisms involved in their degeneration are still unclear. Focusing on cerebral microvessels in the frontal and anterior temporal lobes and the basal ganglia, we used advanced proteomic and immunohistochemical methods to explore the extent of inflammatory and immune responses in CADASIL subjects compared to similar age normal and other disease controls. There was variable loss of VSMC in medial layers of arteries in white matter as well as the cortex, that could not be distinguished whether NOTCH3 mutations were in the epidermal growth factor (EGFr) domains 1-6 or EGFr7-34. Proteomics of isolated cerebral microvessels showed alterations in several proteins, many associated with endoplasmic reticulum (ER) stress including heat shock proteins. Cerebral vessels with sparsely populated VSMCs also attracted robust accrual of perivascular microglia/macrophages in order CD45
Identifiants
pubmed: 37158955
doi: 10.1186/s40478-023-01558-1
pii: 10.1186/s40478-023-01558-1
pmc: PMC10169505
doi:
Substances chimiques
Intercellular Adhesion Molecule-1
126547-89-5
Complement System Proteins
9007-36-7
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
76Subventions
Organisme : NIA NIH HHS
ID : RF1NS110048
Pays : United States
Organisme : Medical Research Council
ID : G0500247
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0400074
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Informations de copyright
© 2023. The Author(s).
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