Alzheimer’s disease is a neurodegenerative disease characterized by disrupted memory, learning functions, reduced life expectancy, and locomotor dysfunction, as a result of the accumulation and aggregation of amyloid peptides that cause neuronal damage in neuronal circuits. In the current study, we exploited a transgenic Drosophila melanogaster line, expressing amyloid-β peptides to investigate the efficacy of a newly synthesized acetylcholinesterase inhibitor, named XJP-1, as a potential AD therapy. Behavioral assays and confocal microscopy were used to characterize the drug effect on AD symptomatology and amyloid peptide deposition. The symptomatology induced in this particular transgenic model recapitulates the scenario observed in human AD patients, showing a shortened lifespan and reduced locomotor functions, along with a significant accumulation of amyloid plaques in the brain. XJP-1 treatment resulted in a significant improvement of AD symptoms and a reduction of amyloid plaques by diminishing the amyloid aggregation rate. In comparison with clinically effective AD drugs, our results demonstrated that XJP-1 has similar effects on AD symptomatology, but at 10 times lower drug concentration than donepezil. It also showed an earlier beneficial effect on the reduction of amyloid plaques at 10 days after drug treatment, as observed for donepezil at 20 days, while the other drugs tested have no such effect. As a novel and potent AChE inhibitor, our study demonstrates that inhibition of the enzyme AChE by XJP-1 treatment improves the amyloid-induced symptomatology in Drosophila, by reducing the number of amyloid plaques within the fruit fly CNS. Thus, compound XJP-1 has the therapeutic potential to be further investigated for the treatment of AD.
Approximately 90% of cancer related deaths can be attributed to a tumour's ability to spread. We have identified CG7379, the fly orthologue of human ING1, as a potent invasion suppressor. ING1 is a type II tumour suppressor with well-established roles in the transcriptional regulation of genes that control cell proliferation, response to DNA damage, oncogene-induced senescence and apoptosis. Recent work suggests a possible role for ING1 in cancer cell invasion and metastasis, but the molecular mechanism underlying this observation is lacking. Our results show that reduced expression of CG7379 promotes invasion in vivo in Drosophila, reduces the junctional localisation of several adherens and septate junction components, and severely disrupts cell-cell junction architecture. Similarly, ING1 knockdown significantly enhances invasion in vitro and disrupts E-cadherin distribution at cell-cell junctions. A transcriptome analysis reveals that loss of ING1 affects the expression of several junctional and cytoskeletal modulators, confirming ING1 as an invasion suppressor and a key regulator of cell-cell junction integrity.
Approximately 90% of cancer-related deaths can be attributed to a tumour's ability to spread. We have identified CG7379, the fly orthologue of human ING1, as a potent invasion suppressor. ING1 is a type II tumour suppressor with well-established roles in the transcriptional regulation of genes that control cell proliferation, response to DNA damage, oncogene-induced senescence and apoptosis. Recent work suggests a possible role for ING1 in cancer cell invasion and metastasis, but the molecular mechanism underlying this observation is lacking. Our results show that reduced expression of CG7379 promotes invasion in vivo in Drosophila , reduces the junctional localization of several adherens and septate junction components, and severely disrupts cell–cell junction architecture. Similarly, ING1 knockdown significantly enhances invasion in vitro and disrupts E-cadherin distribution at cell–cell junctions. A transcriptome analysis reveals that loss of ING1 affects the expression of several junctional and cytoskeletal modulators, confirming ING1 as an invasion suppressor and a key regulator of cell–cell junction integrity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.