Implicative role of cytokines in neuroinflammation mediated AD and associated signaling pathways: Current progress in molecular signaling and therapeutics
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Date
2023-10-30T00:00:00
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Publisher
Elsevier Ireland Ltd
Abstract
Alzheimer's Disease (AD) is one of the most devastating age-related disorder causing significant social and economic burden worldwide. It affects the cognitive and social behavior of individuals and characterized by accumulation of A?, phosphorylated tau and cytokines formation. The synthesis and release of cytokines are regulated by specific groups of immune and non-immune cells in response to microglia or astrocyte activation through multiple pathways. Physiologically, microglia assert an anti-inflammatory, quiescent state with minimal cytokine expression and little phagocytic activity in motion to carry out their housekeeping role to eliminate pathogens, aggregated A? and tau protein. However, they develop a phagocytic nature and overexpress cytokine gene modules in response to certain stimuli in AD. Microglia and astrocytes upon chronic activation release an enormous amount of inflammatory cytokines due to interaction with formed A? and neurofibrillary tangle. Gut microbiota dysbiosis also stimulates the release of inflammatory cytokines contributing to AD pathogenesis. In addition, the dysregulation of few signaling pathways significantly influences the development of disease, and the pace of advancement also rises with age. This review sheds light on multiple pathways results into neuroinflammation triggered by activated cytokines worsening AD pathology and making it an appropriate target for AD treatment. This review also included drugs targeting different neuroinflammation pathways under clinical and preclinical studies that are found to be effective in attenuating the disease pathology. � 2023 Elsevier B.V.
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Keywords
Astrocytes, A?, Cytokines, Drugs, Gut microbiota�brain axis, Interleukin, Microglia, Neuroinflammation