Monomeric C-reactive protein-a key molecule driving development of Alzheimer's disease associated with brain ischaemia?
Por:
Slevin, M, Matou, S, Zeinolabediny, Y, Corpas, R, Weston, R, Liu, D, Boras, E, Di Napoli, M, Petcu, E, Sarroca, S, Popa-Wagner, A, Love, S, Font, MA, Potempa, LA, Al-Baradie, R, Sanfeliu, C, Revilla, S, Badimon, L, Krupinski, J
Publicada:
3 sep 2015
Resumen:
Alzheimer's disease (AD) increases dramatically in patients with ischaemic stroke. Monomeric C-reactive protein (mCRP) appears in the ECM of ischaemic tissue after stroke, associating with microvasculature, neurons and AD-plaques, A beta, also, being able to dissociate native-CRP into inflammatory, mCRP in vivo. Here, mCRP injected into the hippocampal region of mice was retained within the retrosplenial tract of the dorsal 3rd ventrical and surrounding major vessels. Mice developed behavioural/cognitive deficits within 1 month, concomitant with mCRP staining within abnormal looking neurons expressing p-tau and in beta-amyloid 1-42-plaque positive regions. mCRP co-localised with CD105 in microvessels suggesting angiogenesis. Phospho-arrays/Western blotting identified signalling activation in endothelial cells and neurons through p-IRS-1, p-Tau and p-ERK1/2-which was blocked following pre-incubation with mCRP-antibody. mCRP increased vascular monolayer permeability and gap junctions, increased NCAM expression and produced haemorrhagic angiogenesis in mouse matrigel implants. mCRP induced tau244-372 aggregation and assembly in vitro. IHC study of human AD/stroke patients revealed co-localization of mCRP with A beta plaques, tau-like fibrils and IRS-1/P-Tau positive neurons and high mCRP-levels spreading from infarcted core regions matched reduced expression of A beta/Tau. mCRP may be responsible for promoting dementia after ischaemia and mCRP clearance could inform therapeutic avenues to reduce the risk of future dementia.
Filiaciones:
Slevin, M:
Manchester Metropolitan Univ, Sch Healthcare Sci, Manchester M1 5GD, Lancs, England
Univ Med & Pharm, Targu Mures, Romania
Griffith Univ, Dept Pathol Med, Brisbane, Qld 4111, Australia
Matou, S:
Manchester Metropolitan Univ, Sch Healthcare Sci, Manchester M1 5GD, Lancs, England
Zeinolabediny, Y:
Manchester Metropolitan Univ, Sch Healthcare Sci, Manchester M1 5GD, Lancs, England
Corpas, R:
CSIC, Inst Invest Biomed Barcelona, Barcelona, Spain
Weston, R:
Manchester Metropolitan Univ, Sch Healthcare Sci, Manchester M1 5GD, Lancs, England
Liu, D:
Manchester Metropolitan Univ, Sch Healthcare Sci, Manchester M1 5GD, Lancs, England
Boras, E:
Manchester Metropolitan Univ, Sch Healthcare Sci, Manchester M1 5GD, Lancs, England
Di Napoli, M:
San Camillo de Lellis Gen Hosp, Neurol Serv, Rieti, Italy
Petcu, E:
Griffith Univ, Dept Pathol Med, Brisbane, Qld 4111, Australia
Sarroca, S:
CSIC, Inst Invest Biomed Barcelona, Barcelona, Spain
Popa-Wagner, A:
Med Univ Greifswald, Neurol Clin, Greifswald, Germany
Love, S:
Univ Bristol, Sch Clin Sci, Inst Clin Neurosci, Dept Neuropathol, Bristol BS16 1LE, Avon, England
Font, MA:
Hosp Santa Creu & Sant Pau, CSIC ICCC, Barcelona, Spain
Potempa, LA:
Acphazin Inc, Deerfield, IL USA
Al-Baradie, R:
Al Majmaah Univ, Coll Appl Med Sci, Majmaah City, Saudi Arabia
Sanfeliu, C:
CSIC, Inst Invest Biomed Barcelona, Barcelona, Spain
Revilla, S:
CSIC, Inst Invest Biomed Barcelona, Barcelona, Spain
Badimon, L:
Hosp Santa Creu & Sant Pau, CSIC ICCC, Barcelona, Spain
Krupinski, J:
Hosp Univ Mutua Terrassa, Dept Neurol, Terrassa, Barcelona, Spain
Gold, Green Published, Green Accepted
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