Mesenchymal stem cells and cell-derived extracellular vesicles protect hippocampal neurons from oxidative stress and synapse damage induced by amyloid-ß oligomers.
J Biol Chem
; 293(6): 1957-1975, 2018 02 09.
Article
en En
| MEDLINE
| ID: mdl-29284679
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-ß peptide (AßOs) 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 AßOs 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 AßO-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 AßOs; 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Sinapsis
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Péptidos beta-Amiloides
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Estrés Oxidativo
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Células Madre Mesenquimatosas
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Enfermedad de Alzheimer
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Vesículas Extracelulares
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Hipocampo
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Neuronas
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
J Biol Chem
Año:
2018
Tipo del documento:
Article