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2015-03-03

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Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/172894

Abnormal expression and distribution of MMP2 at initial stages of Alzheimer's disease-related pathology

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https://doi.org/10.3233/JAD-142460

Abstract

Previous studies have shown that metalloproteinases (MMPs) participate in the clearance of amyloid-β (Aβ) in Alzheimer's disease (AD); MMP2 and MMP3 cleave soluble Aβ, and both MMP9 and MT1-MMP are able to degrade soluble and fibrillar forms of Aβ. The present study shows increased expression levels of active MMP2 in the entorhinal cortex at early stages of AD-related pathology (Braak and Braak stages I/II-0 and III/IV-A) as revealed by western blotting and gelatin zymography. Confocal microscopy discloses co-localization of MMP2 and phospho-tau in neurofibrillary tangles and dystrophic neurites. MMP2 has the capacity to cleave recombinant tau in vitro in a dose-dependent manner, consistent with a physiological function of MMP2 in normal tau proteolysis. However, MMP2 does not cleave hyperphosphorylated and dephosphorylated tau from enriched paired helical filament fractions. These observations raise the possibility that accumulation of MMP2 in neurofibrillary tangles and concomitant loss of proteolytic capacity on tau protein is a response geared to eliminating production of toxic truncated tau species in AD brains. Keywords: Alzheimer's disease, metalloproteinases, MMP2, neurofibrillary tangles, tau

Subject

Malaltia d'Alzheimer, Patologia, Amiloïdosi, Pèptids, Metabolisme, Metal·loproteïnases, Neurofibromatosi

Subject (English)

Alzheimer's disease, Pathology, Amyloidosis, Peptides, Metabolism, Metalloproteinases, Neurofibromatosis

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Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citation

TERNI, Beatrice and FERRER, Isidro (Ferrer Abizanda). Abnormal expression and distribution of MMP2 at initial stages of Alzheimer's disease-related pathology. Journal of Alzheimer's Disease. 2015. Vol. 46, num. 2, pags. 461-469. ISSN 1387-2877. [consulted: 12 of August of 2026]. Available at: https://hdl.handle.net/2445/172894

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