Pyroptosis is a recently characterized inflammatory form of programmed cell death executed by a family of pore-forming proteins called gasdermins. Upon activation, gasdermins form cell transmembrane pores, which release proinflammatory cytokines and alarmins and cause lytic cell death. Of note, gasdermins can also target intracellular organelle membranes such as the mitochondria to cause mitochondrial permeability transition and release of intracellular stimulators like mitochondrial DNA, ROS, Ca2+, and cytochrome c. Gasdermins-mediated pyroptosis is a multi-pathway cellular event that can be generally divided into four types, namely canonical caspase-1 pathway, non-canonical caspase-4/5/11 pathway, apoptosis protein caspase-3/8-mediated pathway and granzyme-mediated pathway.
Accumulating evidence suggests that pyroptosis and its relationship with neuroinflammation are involved in the process of aging as well as pathogenesis of various neurological disorders including age-related neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, stroke, traumatic brain injury, epilepsy, and sepsis-associated encephalopathy. In addition, therapeutic strategies for the inhibition of pyroptosis pathways have been shown a great promise in multiple preclinical models of neurological disease. Some known compounds include the inhibitors of proinflammatory caspases and NLRP3 Inflammasome. However, specific inhibitors that directly block the function of pore-forming gasdermins are yet to be discovered.
This Research Topic aims to provide an update on the role of pyroptosis in neurological disorders and its therapeutic approaches. Specific themes include, but are not limited to:
1. The role of pyroptosis in a) aging, b) neurodegenerative diseases, c) stroke
2. The role of pyroptosis in cognitive dysfunction
3. The role of mitochondrial dysfunction in pyroptosis
4. Specific inhibitors that target gasdermins pore-forming process
Pyroptosis is a recently characterized inflammatory form of programmed cell death executed by a family of pore-forming proteins called gasdermins. Upon activation, gasdermins form cell transmembrane pores, which release proinflammatory cytokines and alarmins and cause lytic cell death. Of note, gasdermins can also target intracellular organelle membranes such as the mitochondria to cause mitochondrial permeability transition and release of intracellular stimulators like mitochondrial DNA, ROS, Ca2+, and cytochrome c. Gasdermins-mediated pyroptosis is a multi-pathway cellular event that can be generally divided into four types, namely canonical caspase-1 pathway, non-canonical caspase-4/5/11 pathway, apoptosis protein caspase-3/8-mediated pathway and granzyme-mediated pathway.
Accumulating evidence suggests that pyroptosis and its relationship with neuroinflammation are involved in the process of aging as well as pathogenesis of various neurological disorders including age-related neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, stroke, traumatic brain injury, epilepsy, and sepsis-associated encephalopathy. In addition, therapeutic strategies for the inhibition of pyroptosis pathways have been shown a great promise in multiple preclinical models of neurological disease. Some known compounds include the inhibitors of proinflammatory caspases and NLRP3 Inflammasome. However, specific inhibitors that directly block the function of pore-forming gasdermins are yet to be discovered.
This Research Topic aims to provide an update on the role of pyroptosis in neurological disorders and its therapeutic approaches. Specific themes include, but are not limited to:
1. The role of pyroptosis in a) aging, b) neurodegenerative diseases, c) stroke
2. The role of pyroptosis in cognitive dysfunction
3. The role of mitochondrial dysfunction in pyroptosis
4. Specific inhibitors that target gasdermins pore-forming process
