The data indicates that COX-2 overexpression causes alteration of neuronal cell cycle in a murine model of AD neuropathology, and provides a rational basis for targeting neuronal COX-2 in therapeutic research aimed at slowing the clinical progression of AD.
COX-2 mRNA levels in AD, PD, cerebrovascular disease, and control cases were each significantly lower than in ALS and were not significantly different from each other.
After transfection by PTGS2 and miR-103 mimic plasmid in PC12 cellular AD model, the total neurite growth was shortened compared with miR-103 mimic group, and cells apoptosis was enhanced which indicated PTGS2 mimic attenuated the influence of miR-103 mimic on progression of AD.
The results indicate that while COX-2 remains a major player in propagating inflammmation in AD and in stressed HN cells, COX-3 may play ancillary roles in membrane-based COX signaling or when basal levels of COX-1 or COX-2 expression persist.
These findings suggest that unknown factors besides Abeta deposition are necessary for the cyclooxygenase-2 up-regulation and neurodegeneration in Alzheimer's disease.
The ability of p38 MAPK to augment COX-2 expression in human neuroblastoma cells, as shown here, suggests that p38 MAPK may be involved in neuronal expression of COX-2 in AD.
The results indicate elevated expression of neuronal COX-2 in subregions of the hippocampal formation in AD and that such elevation may potentiate Abeta-mediated oxidative stress.
As our sample size was limited, large-scale, well-designed studies are necessary to validate the association between the COX-2 765G>C polymorphism and AD.
Although the levels of COX-2 and its metabolic product prostaglandin (PG)E2 are elevated in the brain of AD patients, the mechanisms for the development of AD remain unknown.
Moreover, the expression of both COX-2 and PLA2 appears to be strongly activated during Alzheimer's disease (AD), indicating the importance of inflammatory gene pathways as a response to brain injury.
These results suggest that COX-2 expression may be differentially regulated among subdivisions of the hippocampus and that elevated COX-2 expression in the CA1 of AD brains may be associated with AD pathology and thus cognitive dysfunction.
Based on our findings, it is unlikely that neuronal COX-2 contributes to pathology in end stage AD; however, COX-2 in other cell types may participate in the inflammation-related response associated with the disease.
We concluded that 1) Tg mice showed a behavioral dysfunction in the water maze test, 2) levels of hPS2, Abeta-42, caspase-3, and Cox-2 expression were modulated in the brains of both Tg mice, 3) dense staining with antibody to hPS2, Abeta-42, caspase-3, and Cox-2 was visible in the brains of Tg mice compared with age-matched control mice, and 4) distinguishable AD phenotypes between hPS2w- and hPS2m-Tg mice did not appear.
In conclusion, the present results suggest that in DLB nigral COX-2 mRNA expression does not correlate with dopaminergic neurodegeneration and that the slight changes observed in the common type are probably due to the concomitant AD pathology.
Tackling neuroinflammation and cholinergic deficit in Alzheimer's disease: Multi-target inhibitors of cholinesterases, cyclooxygenase-2 and 15-lipoxygenase.
The great interest of the researchers in this field is due to the importance of selective COX-2 inhibitors as a relatively safe and effective set of compounds which could present different properties such as antirheumatic, anti-inflammatory, antiplatelet, anti-Alzheimer's disease, anti-Parkinson's disease, and anticancer.
In conclusion, the present results suggest that in DLB nigral COX-2 mRNA expression does not correlate with dopaminergic neurodegeneration and that the slight changes observed in the common type are probably due to the concomitant AD pathology.
These findings suggest that unknown factors besides Abeta deposition are necessary for the cyclooxygenase-2 up-regulation and neurodegeneration in Alzheimer's disease.
Because the inhibition of COX-1 is also known to cause tissue damage in the gastrointestinal system from the resultant reduced cytoprotection, selective COX-2 inhibitors are being investigated and tested clinically as potentially better therapeutics for AD patients.
These data suggest that basic gene induction mechanisms, which have been conserved over long periods of evolution, that increase NF-kappaB-DNA binds ing may be fundamental in driving transcription from inflammation-related genes, such as COX-2, that operate in stressed tissues, in normally aging cell lines, and in neurodegenerative disorders that include AD brain.