Stroke (Brain Attack)
Stroke is the world's second leading cause of mortality, with a high incidence of severe morbidity in surviving victims. Currently, there are relatively few treatment options available to minimize tissue death following a stroke. The pathophysiology of stroke is complex and involves numerous processes such as energy failure, acidosis, increased intracellular calcium levels, excitotoxicity, generation of arachidonic acid products, cytokine-mediated cytotoxicity, complement activation, disruption of the blood-brain barrier (BBB), activation of glial cells, etc.
An increasing number of studies have indicated a key role of NLRP3 inflammasome in ischemic stroke. Targeting upstream or downstream of the NLRP3 inflammasome pathway at the molecular level, including modulating protein expression, assembly, activation and/or secretion, may have a promising prospect in developing novel therapeutic agents for ischemic stroke. Core proteins involved in the NF-κB and MAPK pathways, proteins of the NLRP3 inflammasome complex, plasma membrane receptors or channels, cytokines (IL-1β and IL-18) and their receptors may serve as the potential therapeutic targets for ischemic stroke.
Fig.1 Activation of the NLRP3 inflammasome signaling pathway in ischemic stroke. (Ma, 2018)
A number of common and significant molecular and cellular responses related to post-ischemia have been studied, such as up-regulated gene expression and apoptosis. Thus, interruption of these processes by antagonizing some potential protein targets may contribute to the improvement of novel stroke therapies. Current therapeutic targets for stroke treatment play a variety of biological functions in stroke process, such as acetylcholinesterase (AChE), angiotensin I converting enzyme 2 (ACE2), P2Y purinoceptor 12 (P2Y12), postsynaptic density protein 95 (PSD-95), peroxisome proliferator-activated receptor gamma (PPAR-γ), and plasminogen activator inhibitor-1 (PAI-1).
|PPAR-γ||P2Y12||NLRP3||Coagulation factor X|
|PSD-95||P53||PARP1||Coagulation factor II|
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- Ma, C.; et al. Evidence and perspective for the role of the NLRP3 inflammasome signaling pathway in ischemic stroke and its therapeutic potential. International journal of molecular medicine. 2018, 42(6): 2979-2990.