Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004364 (autoimmune disease)
 24,845 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiple sclerosis (MS) is a progressive chronic inflammatory autoimmune disease of the myelin sheath, and melatonin is a powerful antioxidant and anti-inflammatory agent. The present study evaluated the protective effect of melatonin on demyelination and remyelination processes in male and female mice with experimental MS induced by cuprizone. This model of experimental MS in mice is widely used because cuprizone administration causes an artificial demyelination reaction through oligodendrocyte apoptosis, while its withdrawal leads to spontaneous remyelination. Male and female SWR/J mice (n = 78) were divided into three main groups (control, cuprizone, and cuprizone + melatonin), which were each further subdivided into males and females. Cuprizone was orally administered at a dose of 400 mg/kg/day by oral gavage for 5 weeks. In addition, melatonin was intraperitoneally administered for 9 weeks at a dose of 80 mg/kg/day. During the demyelination stage, melatonin exhibited a neuroprotective function in both male and female mice. This was evidenced by improved locomotor activity, increased antioxidant levels (catalase, superoxide dismutase, glutathione peroxidase, and glutathione), and reduced levels of malondialdehyde and inflammatory factors (interleukin-1 beta and tumor necrosis factor-alpha) in male and female mice. However, the effect of melatonin during the remyelination stage varied between sexes; male mice experienced protective effects following melatonin administration, whereas no effect was observed in female mice. These results suggest a complex interaction involving exogenous melatonin, remyelination, and endogenous female sex hormones.
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PMID:Neuroprotective Effects of Melatonin during Demyelination and Remyelination Stages in a Mouse Model of Multiple Sclerosis. 3171 52

Multiple sclerosis (MS) is a chronic, inflammatory, and neurodegenerative autoimmune disease. MS is a devastating disorder that is characterized by cognitive and motor deficits. Cuprizone-induced demyelination is the most widely experimental model used for MS. Cuprizone is a copper chelator that is well characterized by microgliosis and astrogliosis and is reproducible for demyelination and remyelination. Secukinumab (SEC) is a fully human monoclonal anti-human antibody of the IgG1/kappa isotype that selectively targets IL-17A. Expression of IL-17 is associated with MS. Also, IL-17 stimulates microglia and astrocytes resulting in progression of MS through chemokine production and neutrophil recruitment. This study aimed to investigate the neuroprotective effects of SEC on cuprizone-induced demyelination with examining the underlying mechanisms. Locomotor activity, short-term spatial memory function, staining by Luxol Fast Blue, myelin basic protein, gliasosis, inflammatory, and oxidative-stress markers were assessed to evaluate neuroprotective, anti-inflammatory and antioxidant effects. Moreover, the safety profile of SEC was evaluated. The present study concludes the efficacy of SEC in Cup-induced demyelination experimental model. Interestingly, SEC had neuroprotective and antioxidant effects besides its anti-inflammatory effect in the studied experimental model of MS. Graphical abstract.
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PMID:Repurposing of Secukinumab as Neuroprotective in Cuprizone-Induced Multiple Sclerosis Experimental Model via Inhibition of Oxidative, Inflammatory, and Neurodegenerative Signaling. 3251 62

Multiple sclerosis is a progressive autoimmune disorder of the myelin sheath and is the most common inflammatory disease of young adults. Up to 65% of multiple sclerosis patients have cognitive impairments such as memory loss and difficulty in understanding and maintaining attention and concentration. Many pharmacological interventions have been used to reverse motor impairments in multiple sclerosis patients; however, none of these drugs improve cognitive function. Melatonin can diffuse through the blood-brain barrier and has well-known antioxidant and anti-inflammatory properties with almost no side effects; it is, therefore, a promising neuroprotective supplement for many neurological diseases, such as multiple sclerosis, Alzheimer's disease, Parkinson's disease, ischemic stroke, and fibromyalgia. However, only some researches have assessed the effect of melatonin on cognitive dysfunction in multiple sclerosis. Here, we evaluated the effects of melatonin supplementation on memory defects induced by cuprizone in a mouse model of multiple sclerosis. Cuprizone (400 mg/kg) and melatonin (80 mg/kg) were administered to SWR/J mice daily for 5 weeks. Open field, tail-flick, and novel object recognition behavioral tests were performed. Also, expression of cAMP-response element-binding protein, synaptophysin, and postsynaptic density protein 95 were measured in the prefrontal cortex. Melatonin significantly improved the memory defects induced by cuprizone toxicity by up-regulating cAMP-response element-binding protein and by increasing expression of the synapse-associated synaptophysin and postsynaptic density protein 95 genes in the prefrontal cortex. These results indicate that melatonin may provide protective effects against memory impairments associated with multiple sclerosis.
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PMID:Melatonin improves memory defects in a mouse model of multiple sclerosis by up-regulating cAMP-response element-binding protein and synapse-associated proteins in the prefrontal cortex. 3270 87