Int J Med Sci
2015; 12(1):48-56.
doi:10.7150/ijms.10035 This issueCite
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.
✉ Corresponding author: Soraya L. Valles, Ph.D. Department of Physiology. School of Medicine. University of Valencia. Blasco Ibañez, 15. 46010 Valencia, Spain. Telf: 34-96-3864646. Fax: 34-96-3864642. Email: lilian.valleses.
Citation:
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. https://www.medsci.org/v12p0048.htm
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.
Aguirre-Rueda, D., Guerra-Ojeda, S., Aldasoro, M., Iradi, A., Obrador, E., Ortega, A., Mauricio, M.D., Vila, J.M., Valles, S.L. (2015). Astrocytes Protect Neurons from Aβ1-42 Peptide-Induced Neurotoxicity Increasing TFAM and PGC-1 and Decreasing PPAR-γ and SIRT-1. International Journal of Medical Sciences, 12(1), 48-56. https://doi.org/10.7150/ijms.10035.
ACS
Aguirre-Rueda, D.; Guerra-Ojeda, S.; Aldasoro, M.; Iradi, A.; Obrador, E.; Ortega, A.; Mauricio, M.D.; Vila, J.M.; Valles, S.L. 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.
NLM
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. https://www.medsci.org/v12p0048.htm
CSE
Aguirre-Rueda D, Guerra-Ojeda S, Aldasoro M, Iradi A, Obrador E, Ortega A, Mauricio MD, Vila JM, Valles SL. 2015. 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. 12(1):48-56.