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J Biol Chem. 2018 Feb 9;293(6):1957-1975. doi: 10.1074/jbc.M117.807180. Epub 2017 Dec 28.

Mesenchymal stem cells and cell-derived extracellular vesicles protect hippocampal neurons from oxidative stress and synapse damage induced by amyloid-β oligomers.

Author information

1
From the Institute of Biophysics Carlos Chagas Filho.
2
the Institute of Medical Biochemistry Leopoldo de Meis, and.
3
the National Center for Structural Biology and Bioimaging/CENABIO, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21944-590, Brazil.
4
From the Institute of Biophysics Carlos Chagas Filho, rmotero@biof.ufrj.br.
5
From the Institute of Biophysics Carlos Chagas Filho, ferreira@bioqmed.ufrj.br.

Abstract

Alzheimer's disease (AD) is a disabling and highly prevalent neurodegenerative condition, for which there are no effective therapies. Soluble oligomers of the amyloid-β peptide (AβOs) are thought to be proximal neurotoxins involved in early neuronal oxidative stress and synapse damage, ultimately leading to neurodegeneration and memory impairment in AD. The aim of the current study was to evaluate the neuroprotective potential of mesenchymal stem cells (MSCs) against the deleterious impact of AβOs on hippocampal neurons. To this end, we established transwell cocultures of rat hippocampal neurons and MSCs. We show that MSCs and MSC-derived extracellular vesicles protect neurons against AβO-induced oxidative stress and synapse damage, revealed by loss of pre- and postsynaptic markers. Protection by MSCs entails three complementary mechanisms: 1) internalization and degradation of AβOs; 2) release of extracellular vesicles containing active catalase; and 3) selective secretion of interleukin-6, interleukin-10, and vascular endothelial growth factor to the medium. Results support the notion that MSCs may represent a promising alternative for cell-based therapies in AD.

KEYWORDS:

Alzheimer's disease; amyloid-β; catalase; cytokine action; endocytosis; extracellular vesicles; hippocampus; mesenchymal stem cells (MSCs); oligomers; oxidative stress; synapse

PMID:
29284679
PMCID:
PMC5808759
DOI:
10.1074/jbc.M117.807180

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