International Journal of Medical Sciences

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23 October 2017

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Int J Med Sci 2015; 12(1):48-56. doi:10.7150/ijms.10035

Research Paper

Astrocytes Protect Neurons from Aβ1-42 Peptide-Induced Neurotoxicity Increasing TFAM and PGC-1 and Decreasing PPAR-γ and SIRT-1

Diana Aguirre-Rueda, Sol Guerra-Ojeda, Martin Aldasoro, Antonio Iradi, Elena Obrador, Angel Ortega, M. Dolores Mauricio, Jose Mª Vila, Soraya L. Valles

Department of Physiology. School of Medicine, University of Valencia. Spain.

Abstract

One of the earliest neuropathological events in Alzheimer's disease is accumulation of astrocytes at sites of Aβ1-42 depositions. Our results indicate that Aβ1-42 toxic peptide increases lipid peroxidation, apoptosis and cell death in neurons but not in astrocytes in primary culture. Aβ1-42-induced deleterious neuronal effects are not present when neurons and astrocytes are mixed cultured. Stimulation of astrocytes with toxic Aβ1-42 peptide increased p-65 and decreased IκB resulting in inflammatory process. In astrocytes Aβ1-42 decreases protein expressions of sirtuin 1 (SIRT-1) and peroxisome proliferator-activated receptor γ (PPAR-γ) and over-expresses peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1) and mitochondrial transcription factor A (TFAM), protecting mitochondria against Aβ1-42-induced damage and promoting mitochondrial biogenesis.

In summary our data suggest that astrocytes may have a key role in protecting neurons, increasing neural viability and mitochondrial biogenesis, acquiring better oxidative stress protection and perhaps modulating inflammatory processes against Aβ1-42 toxic peptide. This might be a sign of a complex epigenetic process in Alzheimer's disease development.

Keywords: Alzheimer's Disease, MnSOD, PPAR-γ, TFAM, PGC-1, NF-κB.

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How to cite this article:
Aguirre-Rueda D, Guerra-Ojeda S, Aldasoro M, Iradi A, Obrador E, Ortega A, Mauricio MD, Vila JM, Valles SL. Astrocytes Protect Neurons from Aβ1-42 Peptide-Induced Neurotoxicity Increasing TFAM and PGC-1 and Decreasing PPAR-γ and SIRT-1. Int J Med Sci 2015; 12(1):48-56. doi:10.7150/ijms.10035. Available from http://www.medsci.org/v12p0048.htm