Oxidative Stress during the Progression of β-Amyloid Pathology in the Neocortex of the Tg2576 Mouse Model of Alzheimer’s Disease
Joint Authors
Porcellotti, Sara
Fanelli, Francesca
Fracassi, Anna
Sepe, Sara
Bernardi, Cinzia
Cimini, AnnaMaria
Moreno, Sandra
Cecconi, Francesco
Cerù, Maria Paola
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2015, Issue 2015 (31 Dec. 2015), pp.1-18, 18 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-04-20
Country of Publication
Egypt
No. of Pages
18
Main Subjects
Abstract EN
Alzheimer’s disease (AD) is the most common form of dementia, characterized by progressive neurodegeneration.
Pathogenetic mechanisms, triggered by β-amyloid (Aβ) accumulation, include oxidative stress, derived from energy homeostasis deregulation and involving mitochondria and peroxisomes.
We here addressed the oxidative stress status and the elicited cellular response at the onset and during the progression of Aβ pathology, studying the neocortex of Tg2576 model of AD.
Age-dependent changes of oxidative damage markers, antioxidant enzymes, and related transcription factors were analysed in relation to the distribution of Aβ peptide and oligomers, by a combined molecular/morphological approach.
Nucleic acid oxidative damage, accompanied by defective antioxidant defences, and decreased PGC1α expression are already detected in 3-month-old Tg2576 neurons.
Conversely, PPARα is increased in these cells, with its cytoplasmic localization suggesting nongenomic, anti-inflammatory actions.
At 6 months, when intracellular Aβ accumulates, PMP70 is downregulated, indicating impairment of fatty acids peroxisomal translocation and their consequent harmful accumulation.
In 9-month-old Tg2576 neocortex, Aβ oligomers and acrolein deposition correlate with GFAP, GPX1, and PMP70 increases, supporting a compensatory response, involving astroglial peroxisomes.
At severe pathological stages, when senile plaques disrupt cortical cytoarchitecture, antioxidant capacity is gradually lost.
Overall, our data suggest early therapeutic intervention in AD, also targeting peroxisomes.
American Psychological Association (APA)
Porcellotti, Sara& Fanelli, Francesca& Fracassi, Anna& Sepe, Sara& Cecconi, Francesco& Bernardi, Cinzia…[et al.]. 2015. Oxidative Stress during the Progression of β-Amyloid Pathology in the Neocortex of the Tg2576 Mouse Model of Alzheimer’s Disease. Oxidative Medicine and Cellular Longevity،Vol. 2015, no. 2015, pp.1-18.
https://search.emarefa.net/detail/BIM-1075825
Modern Language Association (MLA)
Porcellotti, Sara…[et al.]. Oxidative Stress during the Progression of β-Amyloid Pathology in the Neocortex of the Tg2576 Mouse Model of Alzheimer’s Disease. Oxidative Medicine and Cellular Longevity No. 2015 (2015), pp.1-18.
https://search.emarefa.net/detail/BIM-1075825
American Medical Association (AMA)
Porcellotti, Sara& Fanelli, Francesca& Fracassi, Anna& Sepe, Sara& Cecconi, Francesco& Bernardi, Cinzia…[et al.]. Oxidative Stress during the Progression of β-Amyloid Pathology in the Neocortex of the Tg2576 Mouse Model of Alzheimer’s Disease. Oxidative Medicine and Cellular Longevity. 2015. Vol. 2015, no. 2015, pp.1-18.
https://search.emarefa.net/detail/BIM-1075825
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1075825