De Godoy 2018 J Biol Chem
|de Godoy MA, Saraiva LM, de Carvalho LRP, Vasconcelos-Dos-Santos A, Beiral HJV, Ramos AB, Silva LRP, Leal RB, Monteiro VHS, Braga CV, de Araujo-Silva CA, Sinis LC, Bodart-Santos V, Kasai-Brunswick TH, Alcantara CL, Lima APCA, da Cunha-E Silva NL, Galina A, Vieyra A, De Felice FG, Mendez-Otero R, Ferreira ST (2018) Mesenchymal stem cells and cell-derived extracellular vesicles protect hippocampal neurons from oxidative stress and synapse damage induced by amyloid-β oligomers. J Biol Chem 293:1957-75.|
de Godoy MA, Saraiva LM, de Carvalho LRP, Vasconcelos-Dos-Santos A, Beiral HJV, Ramos AB, Silva LRP, Leal RB, Monteiro VHS, Braga CV, de Araujo-Silva CA, Sinis LC, Bodart-Santos V, Kasai-Brunswick TH, Alcantara CL, Lima APCA, da Cunha-E Silva NL, Galina A, Vieyra A, De Felice FG, Mendez-Otero R, Ferreira ST (2018) J Biol Chem
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 • Bioblast editor: Kandolf G • O2k-Network Lab: BR Rio de Janeiro Galina A, BR Rio de Janeiro Institute Biomedical Chemistry
Labels: MiParea: Respiration Pathology: Alzheimer's Stress:Oxidative stress;RONS Organism: Rat Tissue;cell: Nervous system Preparation: Intact cells
Coupling state: LEAK, ROUTINE, ET