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Targeting the miRNA-155/TNFSF10 network restrains inflammatory response in the retina in a mouse model of Alzheimer’s disease
- Source :
- Cell Death and Disease, Vol 12, Iss 10, Pp 1-15 (2021), Cell Death & Disease
- Publication Year :
- 2021
- Publisher :
- Nature Publishing Group, 2021.
-
Abstract
- Age-related disorders, such as Alzheimer’s disease (AD) and age-related macular degeneration (AMD) share common features such as amyloid-β (Aβ) protein accumulation. Retinal deposition of Aβ aggregates in AMD patients has suggested a potential link between AMD and AD. In the present study, we analyzed the expression pattern of a focused set of miRNAs, previously found to be involved in both AD and AMD, in the retina of a triple transgenic mouse model of AD (3xTg-AD) at different time-points. Several miRNAs were differentially expressed in the retina of 3xTg-AD mice, compared to the retina of age-matched wild-type (WT) mice. In particular, bioinformatic analysis revealed that miR-155 had a central role in miRNA-gene network stability, regulating several pathways, including apoptotic and inflammatory signaling pathways modulated by TNF-related apoptosis-inducing ligand (TNFSF10). We showed that chronic treatment of 3xTg-AD mice with an anti-TNFSF10 monoclonal antibody was able to inhibit the retinal expression of miR-155, which inversely correlated with the expression of its molecular target SOCS-1. Moreover, the fine-tuned mechanism related to TNFSF10 immunoneutralization was tightly linked to modulation of TNFSF10 itself and its death receptor TNFRSF10B, along with cytokine production by microglia, reactive gliosis, and specific AD-related neuropathological hallmarks (i.e., Aβ deposition and Tau phosphorylation) in the retina of 3xTg-AD mice. In conclusion, immunoneutralization of TNFSF10 significantly preserved the retinal tissue in 3xTg-AD mice, suggesting its potential therapeutic application in retinal degenerative disorders.
- Subjects :
- Cancer Research
medicine.medical_treatment
Retinal Pigment Epithelium
TNF-Related Apoptosis-Inducing Ligand
chemistry.chemical_compound
Gene Regulatory Networks
Gliosis
Phosphorylation
Receptor
Microglia
Microfilament Proteins
Alzheimer's disease
Cell biology
Interleukin-10
medicine.anatomical_structure
Cytokine
Signal transduction
Signal Transduction
Genetically modified mouse
Immunology
Down-Regulation
Mice, Transgenic
tau Proteins
Biology
Retina
Article
Cellular and Molecular Neuroscience
Suppressor of Cytokine Signaling 1 Protein
Alzheimer Disease
microRNA
Glial Fibrillary Acidic Protein
medicine
Animals
Neurodegeneration
Inflammation
Amyloid beta-Peptides
Base Sequence
QH573-671
Tumor Necrosis Factor-alpha
Gene Expression Profiling
Calcium-Binding Proteins
Retinal
Cell Biology
Antibodies, Neutralizing
Disease Models, Animal
MicroRNAs
Receptors, TNF-Related Apoptosis-Inducing Ligand
chemistry
Gene Expression Regulation
Cyclooxygenase 2
Cytology
Subjects
Details
- Language :
- English
- ISSN :
- 20414889
- Volume :
- 12
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Cell Death and Disease
- Accession number :
- edsair.doi.dedup.....9008659169651becacffdcd99e5a7514