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

One of the earliest neuropathological events in Alzheimer's disease is accumulation of astrocytes at sites of Aβ(1-42) depositions. Our results indicate that Aβ(1-42) toxic peptide increases lipid peroxidation, apoptosis and cell death in neurons but not in astrocytes in primary culture. Aβ(1-42)-induced deleterious neuronal effects are not present when neurons and astrocytes are mixed cultured. Stimulation of astrocytes with toxic Aβ(1-42) peptide increased p-65 and decreased IκB resulting in inflammatory process. In astrocytes Aβ(1-42) 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 Aβ(1-42)-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 Aβ(1-42) toxic peptide. This might be a sign of a complex epigenetic process in Alzheimer's disease development.