Back to Search
Start Over
Astrocytes protect neurons from Aβ1-42 peptide-induced neurotoxicity increasing TFAM and PGC-1 and decreasing PPAR-γ and SIRT-1.
- Source :
-
International journal of medical sciences [Int J Med Sci] 2015 Jan 01; Vol. 12 (1), pp. 48-56. Date of Electronic Publication: 2015 Jan 01 (Print Publication: 2015). - Publication Year :
- 2015
-
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.
- Subjects :
- Amyloid beta-Peptides metabolism
Amyloid beta-Peptides pharmacology
Animals
Astrocytes cytology
Caspase 3 metabolism
Cell Death drug effects
Cells, Cultured
Coculture Techniques
Lipid Peroxidation drug effects
Mitochondria drug effects
Mitochondria metabolism
Neurons drug effects
PPAR gamma metabolism
Peptide Fragments metabolism
Peptide Fragments pharmacology
Peroxides metabolism
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Rats
Sirtuin 1 metabolism
Superoxide Dismutase metabolism
Transcription Factor RelA metabolism
Transcription Factors metabolism
Amyloid beta-Peptides toxicity
Astrocytes metabolism
Neurons metabolism
Neurons pathology
Peptide Fragments toxicity
Subjects
Details
- Language :
- English
- ISSN :
- 1449-1907
- Volume :
- 12
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- International journal of medical sciences
- Publication Type :
- Academic Journal
- Accession number :
- 25552918
- Full Text :
- https://doi.org/10.7150/ijms.10035