The vast majority of cells in the human body are capable of secreting exosomes. Exosomes have become an important vehicle for signaling between cells. Exosomes secreted by different cells have some of the structural and functional properties of that cell and thus have different regulatory functions. A large number of recent experimental studies have shown that exosomes from different sources have different regulatory effects on stroke, and the mechanisms still need to be elucidated. Microglia are core members of central intrinsic immune regulatory cells, which play an important regulatory role in the pathogenesis and progression of stroke. M1 microglia cause neuroinflammation and induce neurotoxic effects, while M2 microglia inhibit neuroinflammation and promote neurogenesis, thus exerting a series of neuroprotective effects. It was found that there is a close link between exosomes and microglia polarization, and that exosome inclusions such as microRNAs play a regulatory role in the M1/M2 polarization of microglia. This research reviews the role of exosomes in the regulation of microglia polarization and reveals their potential value in stroke treatment.
Depression, a major public health problem, imposes a significant economic burden on society. Recent studies have gradually unveiled the important role of neuroinflammation in the pathogenesis of depression. Pyroptosis, a programmed cell death mediated by Gasdermins (GSDMs), is also considered to be an inflammatory cell death with links to inflammation. Pyroptosis has emerged as an important pathological mechanism in several neurological diseases and has been found to be involved in several neuroinflammatory-related diseases. A variety of chemical agents and natural products have been found to be capable of exerting therapeutic effects by modulating pyroptosis. Studies have shown that depression is closely associated with pyroptosis and the induced neuroinflammation of relevant brain regions, such as the hippocampus, amygdala, prefrontal cortex neurons, etc., in which the nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome plays a crucial role. This article provides a timely review of recent findings on the activation and regulation of pyroptosis in relation to depression.
In addition to its profound implications in the fight against cancer, pyroptosis have important role in the regulation of neuronal injury. Microglia are not only central members of the immune regulation of the central nervous system (CNS), but are also involved in the development and homeostatic maintenance of the nervous system. Under various pathological overstimulation, microglia pyroptosis contributes to the massive release of intracellular inflammatory mediators leading to neuroinflammation and ultimately to neuronal damages. In addition, microglia pyroptosis lead to further neurological damage by decreasing the ability to cleanse harmful substances. The pathogenic roles of microglia in a variety of CNS diseases such as neurodegenerative diseases, stroke, multiple sclerosis and depression, and many other neurological disorders have been gradually unveiled. In the context of different neurological disorders, inhibition of microglia pyroptosis by targeting NOD-like receptor family pyrin domain containing (NLRP) 3, caspase-1 and gasdermins (GSDMs) by various chemical agents as well as natural products significantly improve the symptoms or outcome in animal models. This study will provide new ideas for immunomodulatory treatment of CNS diseases.
Neurological disorders cause untold human disability and death each year. For most neurological disorders, the efficacy of their primary treatment strategies remains suboptimal. Microglia are associated with the development and progression of multiple neurological disorders. Targeting the regulation of microglia polarization has emerged as an important therapeutic strategy for neurological disorders. Their pro-inflammatory (M1)/anti-inflammatory (M2) phenotype microglia are closely associated with neuronal apoptosis, synaptic plasticity, blood-brain barrier integrity, resistance to iron death, and astrocyte regulation. LncRNA, a recently extensively studied non-coding transcript of over 200 nucleotides, has shown great value to intervene in microglia polarization. It can often participate in gene regulation of microglia by directly regulating transcription or sponging downstream miRNAs, for example. Through proper regulation, microglia can exert neuroprotective effects, reduce neurological damage and improve the prognosis of many neurological diseases. This paper reviews the progress of research linking lncRNAs to microglia polarization and neurological diseases.
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