Background: One of the pathological hallmarks of Alzheimer's disease (AD) is deposits of amyloid beta-peptide (Abeta) in neuritic plaques and cerebral vessels. Immunization of AD mouse models with Abeta reduces Abeta deposits and improves memory and learning deficits. Because recent clinical trials of immunization with Abeta were halted due to brain inflammation that was presumably induced by a T-cell-mediated autoimmune response, vaccination modalities that elicit predominantly humoral immune responses are currently being developed.
Methods: We have nasally immunized a young AD mouse model with an adenovirus vector encoding 11 tandem repeats of Abeta1-6 fused to the receptor-binding domain (Ia) of Pseudomonas exotoxin A (PEDI), AdPEDI-(Abeta1-6)(11), in order to evaluate the efficacy of the vector in preventing Abeta deposits in the brain. We also have investigated immune responses of mice to AdPEDI-(Abeta1-6)(11).
Results: Nasal immunization of an AD mouse model with AdPEDI-(Abeta1-6)(11) elicited a predominant IgG1 response and reduced Abeta load in the brain. The plasma IL-10 level in the AD mouse model was upregulated after immunization and, upon the stimulation with PEDI-(Abeta1-6)(11), marked IL-10 responses were found in splenic CD4(+) T cells from C57BL/6 mice that had been immunized with AdPEDI-(Abeta1-6)(11).
Conclusions: These results suggest that the induction of Th2-biased responses with AdPEDI-(Abeta1-6)(11) in mice is mediated in part through the upregulation of IL-10, which inhibits activation of dendritic cells that dictate the induction of Th1 cells.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2446608 | PMC |
| http://dx.doi.org/10.1002/jgm.993 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Trehalose Inhibits ferroptosis Through Activating SIRT3/SOD2 Signaling Axis and Alleviates Brain Injury After Traumatic Brain Injury.
Neurochem Res
January 2025
Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China.
Trehalose has neuroprotective effects in neurodegenerative diseases. This study aimed to explore the impact of trehalose on traumatic brain injury (TBI) by investigating its role in neuroprotection. The TBI mice model was established utilizing the cortical impact technique followed by trehalose treatment.
View Article and Find Full Text PDFIdentification and Construction of a R-loop Mediated Diagnostic Model and Associated Immune Microenvironment of COPD through Machine Learning and Single-Cell Transcriptomics.
Inflammation
January 2025
Department of Geriatrics, Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China.
Chronic obstructive pulmonary disease (COPD) is a prevalent chronic inflammatory airway disease with high incidence and significant disease burden. R-loops, functional chromatin structure formed during transcription, are closely associated with inflammation due to its aberrant formation. However, the role of R-loop regulators (RLRs) in COPD remains unclear.
View Article and Find Full Text PDFThe molar dose of FAPI administered impacts on the FAP-targeted PET imaging and therapy in mouse syngeneic tumor models.
Eur J Nucl Med Mol Imaging
January 2025
Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430030, China.
Purpose: Since fibroblast activation protein (FAP), one predominant biomarker of cancer associated fibroblasts (CAFs), is highly expressed in the tumor stroma of various epidermal-derived cancers, targeting FAP for tumor diagnosis and treatment has shown substantial potentials in both preclinical and clinical studies. However, in preclinical settings, tumor-bearing mice exhibit relatively low absolute FAP expression levels, leading to challenges in acquiring high-quality PET images using radiolabeled FAP ligands (FAPIs) with low molar activity, because of which a saturation effect in imaging is prone to happen. Moreover, how exactly the molar dose of FAPI administered to a mouse influences the targeted PET imaging and radiotherapy remains unclear now.
View Article and Find Full Text PDFTranscriptional regulation of the piRNA pathway by Ovo in animal ovarian germ cells.
Genes Dev
December 2024
Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, United Kingdom
The gene-regulatory mechanisms controlling the expression of the germline PIWI-interacting RNA (piRNA) pathway components within the gonads of metazoan species remain largely unexplored. In contrast to the male germline piRNA pathway, which in mice is known to be activated by the testis-specific transcription factor A-MYB, the nature of the ovary-specific gene-regulatory network driving the female germline piRNA pathway remains a mystery. Here, using as a model, we combined multiple genomics approaches to reveal the transcription factor Ovo as regulator of the germline piRNA pathway in ovarian germ cells.
View Article and Find Full Text PDFE3 ligase substrate adaptor SPOP fine-tunes the UPR of pancreatic β cells.
Genes Dev
December 2024
Institute for Diabetes, Obesity, and Metabolism, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19146, USA;
The Cullin-3 E3 ligase adaptor protein SPOP targets proteins for ubiquitination and proteasomal degradation. We previously established the β-cell transcription factor (TF) and human diabetes gene PDX1 as an SPOP substrate, suggesting a functional role for SPOP in the β cell. Here, we generated a β-cell-specific deletion mouse strain ( ) and found that is necessary to prevent aberrant basal insulin secretion and for maintaining glucose-stimulated insulin secretion through impacts on glycolysis and glucose-stimulated calcium flux.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!