title: Astrocytes protect neurons from Aβ1-42 peptide-induced neurotoxicity increasing TFAM and PGC-1 and decreasing PPAR-γ and SIRT-1.
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.
authors.affiliation: Department of Physiology. School of Medicine, University of Valencia. Spain.
authors.forename: Diana
authors.initials: D
authors.lastname: Aguirre-Rueda
authors.affiliation: Department of Physiology. School of Medicine, University of Valencia. Spain.
authors.forename: Sol
authors.initials: S
authors.lastname: Guerra-Ojeda
authors.affiliation: Department of Physiology. School of Medicine, University of Valencia. Spain.
authors.forename: Martin
authors.initials: M
authors.lastname: Aldasoro
authors.affiliation: Department of Physiology. School of Medicine, University of Valencia. Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Iradi
authors.affiliation: Department of Physiology. School of Medicine, University of Valencia. Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Obrador
authors.affiliation: Department of Physiology. School of Medicine, University of Valencia. Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Ortega
authors.affiliation: Department of Physiology. School of Medicine, University of Valencia. Spain.
authors.forename: M Dolores
authors.initials: MD
authors.lastname: Mauricio
authors.affiliation: Department of Physiology. School of Medicine, University of Valencia. Spain.
authors.forename: Jose Ma
authors.initials: JM
authors.lastname: Vila
authors.affiliation: Department of Physiology. School of Medicine, University of Valencia. Spain.
authors.forename: Soraya L
authors.initials: SL
authors.lastname: Valles
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D047495:PPAR gamma / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity*; D010545:Peroxides / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D051381:Rats; D056564:Sirtuin 1 / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D047495:PPAR gamma; D010446:Peptide Fragments; D010545:Peroxides; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; C498145:Rela protein, rat; C489030:Tfam protein, rat; D051996:Transcription Factor RelA; D014157:Transcription Factors; C075222:amyloid beta-protein (1-42); C090308:amyloid beta-protein (40-1); D013482:Superoxide Dismutase; D053148:Caspase 3; C488368:Sirt1 protein, rat; D056564:Sirtuin 1
keywords: Alzheimer's Disease; MnSOD; NF-κB.; PGC-1; PPAR-γ; TFAM