The S100 protein is one of the calcium-binding proteins associated with Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. S100 proteins are expressed in the central nervous system by oligodendrocytes, astrocytes and neurons during both normal and disease conditions. Although amyloid-beta aggregation and hyperphosphorylated tau plaques are the main pathological hallmarks of Alzheimer’s disease, the S100 protein family is closely associated with neuroinflammation in several neurodegenerative disorders, such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis in addition to various types of cancer and other brain diseases. This review aims to present the key role of S100 proteins and their different relevant isoforms, along with the various approaches used for the regulation of these proteins in several neurodegenerative disorders.
Background: Microglial overactivation promotes the production of various second messengers and inflammatory markers in brain tissue, resulting in neuroinflammation and neurodegeneration, which may lead to cognitive decline. The cyclic nucleotides are one of the important second messengers involved in the regulation of neurogenesis, synaptic plasticity, and cognition. The levels of these cyclic nucleotides are maintained by phosphodiesterase enzyme isoforms, particularly PDE4B, in the brain. An imbalance between PDE4B levels and cyclic nucleotides may lead to aggravating neuroinflammation. Methods: Lipopolysaccharides (LPS) were administered intraperitoneally on alternate days for 7 days at a dose of 500 µg/kg in mice, which triggered systemic inflammation. This may lead to the activation of glial cells and may activate oxidative stress and neuroinflammatory markers in brain tissue. Furthermore, oral administration of roflumilast (0.1, 0.2, and 0.4 mg/kg) in this model ameliorated oxidative stress markers, neuroinflammation and improved neurobehavioral parameters in these animals. Results: The detrimental effect of LPS increased oxidative stress, AChE enzyme levels, and decreased catalase levels in brain tissues, along with memory impairment in animals. Moreover, it also enhanced the activity and expression of the PDE4B enzyme, resulting in a decline in cyclic nucleotide levels. Furthermore, treatment with roflumilast improved the cognitive decline, decreased AChE enzyme level, and increased the catalase enzyme level. Roflumilast also reduced the PDE4B expression in a dose-dependent manner, which LPS up-regulated. Conclusion: Roflumilast has shown an anti-neuroinflammatory effect and reversed the cognitive decline in LPS-induced mice model.
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.