Background and purpose
Despite significant advances in Parkinson’s disease (PD), it remains incurable due to limited treatment options. Currently, reused safe drugs already being tested have emerged as effective treatment strategies for a variety of neurodegenerative diseases, including PD. Using a drug supplement approach, the current study investigated the neural evolution potential of compounds mimicking 5-nonroxytryptamine oxalate (5-NOT) and epirubicin (EPI) anticancer drugs treated with cells in cells that are patients with 1-methyl-4-phenylpyridinium (MPP+) and shuubicin (EPI) polysialic acids of shuubicin (EPI).
method
An excitation toxicity model was established by exposing SH-SY5Y cells to 500 µM MPP+ and then treating them with the test compounds. The effects of MPP+-induced toxicity on cell and nuclear morphology, as well as neuroplasticity and expression of cell survival proteins, were studied by immunostaining, gelatin dimograms, and Western blot assays.
result
Treatment with 5-NOT and EPI significantly promoted the survival of MPP+challeged SH-SY5Y cells, preventing changes in cellular and nuclear morphology by regulating the expression of microtubule-associated proteins (MAP-2) and polysialic acid neutral cell adhesion molecules (PSA-NCAM) and NCAM synaptic plastic proteins. Furthermore, 5-NOT and EPI treatment also protected SH-SY5Y cells by restoring levels of nitric oxide, matrix metalloproteinase, and stress-responsive proteins. Five non-MPP+-induced toxicities were attenuated in SH-SY5Y cells by regulating the reflex protein kinase AKT/BAD apoptotic pathway and the P-38 MAP kinase synaptic plasticity pathway.
Conclusion
Current data provide compelling evidence for five potential beneficial roles as candidate glime mimetic drugs targeting neurodegeneration of dopamine neurons, which is characteristic of patients suffering from PD. The results of this study are also supported by previous findings of neurodegenerative diseases in spinal cord injury (in vivo studies) and in vitro models of glutamate-induced excitotoxicity. Identification of novel compounds from small molecule libraries that mimic PSA functions may provide a new therapeutic tool for PD and other neurodegenerative diseases.
sauce:
Journal Reference:
Kalotra, S&Kaur, G. (2025). Reuse 5-nonioxytryptamine and epirubicin as polysialic acid mimetics to protect against MPP+-induced cytotoxicity in human neurons. Journal of exploratory research in pharmacology. doi.org/10.14218/jerp.2024.00038.
