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Pyroptosis,and its Role in Central Nervous System Disease

Institution:	1. Pediatric Research Institute, The Second Affiliated Hospital and Yuying Children''s Hospital of Wenzhou Medical University, Wenzhou 325027, China;2. Children''s Heart Center, Institute of Cardiovascular Development and Translational Medicine, The Second Affiliated Hospital and Yuying Children''s Hospital of Wenzhou Medical University, Wenzhou 325027, China;3. University of Maryland School of Medicine, Baltimore, MD 21201, USA;4. Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children''s Hospital of Wenzhou Medical University, Wenzhou 325027, China;5. Pharmacology, School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang Province, China;6. Department of Cardiology, Zhuji People''s Hospital of Zhejiang Province, Shaoxing 311800, China;7. Comprehensive Breast Health Center, Department of Thyroid and Breast Surgery, Lishui People''s Hospital, The Six Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang 323000, China

Abstract:	Pyroptosis is an inflammatory form of cell death executed by transmembrane pore-forming proteins known as gasdermins and can be activated in an inflammasome-dependent or -independent manner. Inflammasome-dependent pyroptosis is triggered in response to pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs) and has emerged as an important player in the pathogenesis of multiple inflammatory diseases, mainly by releasing inflammatory contents. More recently, numerous studies have revealed the intricate mechanisms of pyroptosis and its role in the development of neuroinflammation in central nervous system (CNS) diseases. In this review, we summarize current understandings of the molecular and regulatory mechanisms of pyroptosis. In addition, we discuss how pyroptosis can drive different forms of neurological diseases and new promising therapeutic strategies targeting pyroptosis that can be leveraged to treat neuroinflammation.

Keywords:	gasdermins inflammasomes caspase neuroinflammation neurological diseases PAMPs"} {"#name":"keyword" "$":{"id":"k0035"} "$$":[{"#name":"text" "_":"pathogen-associated molecular patterns DAMPs"} {"#name":"keyword" "$":{"id":"k0045"} "$$":[{"#name":"text" "_":"damage-associated molecular patterns CNS"} {"#name":"keyword" "$":{"id":"k0055"} "$$":[{"#name":"text" "_":"central nervous system AD"} {"#name":"keyword" "$":{"id":"k0065"} "$$":[{"#name":"text" "_":"Alzheimer’s disease PD"} {"#name":"keyword" "$":{"id":"k0075"} "$$":[{"#name":"text" "_":"Parkinson’s disease ALS"} {"#name":"keyword" "$":{"id":"k0085"} "$$":[{"#name":"text" "_":"amyotrophic lateral sclerosis MLKL"} {"#name":"keyword" "$":{"id":"k0095"} "$$":[{"#name":"text" "_":"mixed lineage kinase domain-like protein MS"} {"#name":"keyword" "$":{"id":"k0105"} "$$":[{"#name":"text" "_":"multiple sclerosis ROS"} {"#name":"keyword" "$":{"id":"k0115"} "$$":[{"#name":"text" "_":"reactive oxygen species LPS"} {"#name":"keyword" "$":{"id":"k0125"} "$$":[{"#name":"text" "_":"lipopolysaccharides GSDMD"} {"#name":"keyword" "$":{"id":"k0135"} "$$":[{"#name":"text" "_":"gasdermin D GWAS"} {"#name":"keyword" "$":{"id":"k0145"} "$$":[{"#name":"text" "_":"genome-wide association studies GZMA"} {"#name":"keyword" "$":{"id":"k0155"} "$$":[{"#name":"text" "_":"granzyme A MMP-1"} {"#name":"keyword" "$":{"id":"k0165"} "$$":[{"#name":"text" "_":"matrix metalloproteinases 1 NASH"} {"#name":"keyword" "$":{"id":"k0175"} "$$":[{"#name":"text" "_":"nonalcoholic steatohepatitis FMF"} {"#name":"keyword" "$":{"id":"k0185"} "$$":[{"#name":"text" "_":"familial Mediterranean fever NOMID"} {"#name":"keyword" "$":{"id":"k0195"} "$$":[{"#name":"text" "_":"neonatal-onset multisystem inflammatory disease GZMB"} {"#name":"keyword" "$":{"id":"k0205"} "$$":[{"#name":"text" "_":"granzyme B AE"} {"#name":"keyword" "$":{"id":"k0215"} "$$":[{"#name":"text" "_":"alopecia and excoriation NLR"} {"#name":"keyword" "$":{"id":"k0225"} "$$":[{"#name":"text" "_":"Nod-like receptor ASC"} {"#name":"keyword" "$":{"id":"k0235"} "$$":[{"#name":"text" "_":"apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain EV71"} {"#name":"keyword" "$":{"id":"k0245"} "$$":[{"#name":"text" "_":"enterovirus 71 dsDNA"} {"#name":"keyword" "$":{"id":"k0255"} "$$":[{"#name":"text" "_":"double-stranded DNA OGD/R"} {"#name":"keyword" "$":{"id":"k0265"} "$$":[{"#name":"text" "_":"oxygen glucose deprivation/reperfusion PTX"} {"#name":"keyword" "$":{"id":"k0275"} "$$":[{"#name":"text" "_":"pertussis toxin EAE"} {"#name":"keyword" "$":{"id":"k0285"} "$$":[{"#name":"text" "_":"experimental autoimmune encephalomyelitis CTL"} {"#name":"keyword" "$":{"id":"k0295"} "$$":[{"#name":"text" "_":"cytotoxic T lymphocytes GPX4"} {"#name":"keyword" "$":{"id":"k0305"} "$$":[{"#name":"text" "_":"Glutathione peroxidase 4 TCA"} {"#name":"keyword" "$":{"id":"k0315"} "$$":[{"#name":"text" "_":"tricarboxylic acid cycle TBI"} {"#name":"keyword" "$":{"id":"k0325"} "$$":[{"#name":"text" "_":"traumatic brain injury LPC"} {"#name":"keyword" "$":{"id":"k0335"} "$$":[{"#name":"text" "_":"lysophosphatidylcholine BBB"} {"#name":"keyword" "$":{"id":"k0345"} "$$":[{"#name":"text" "_":"blood–brain barrier CIR"} {"#name":"keyword" "$":{"id":"k0355"} "$$":[{"#name":"text" "_":"cerebral ischemia–reperfusion HIV-1"} {"#name":"keyword" "$":{"id":"k0365"} "$$":[{"#name":"text" "_":"human immunodeficiency virus 1 ZIKV"} {"#name":"keyword" "$":{"id":"k0375"} "$$":[{"#name":"text" "_":"Zika virus NPC"} {"#name":"keyword" "$":{"id":"k0385"} "$$":[{"#name":"text" "_":"neural progenitor cells JEV"} {"#name":"keyword" "$":{"id":"k0395"} "$$":[{"#name":"text" "_":"Japanese encephalitis virus EV-A71"} {"#name":"keyword" "$":{"id":"k0405"} "$$":[{"#name":"text" "_":"enterovirus A71 HD"} {"#name":"keyword" "$":{"id":"k0415"} "$$":[{"#name":"text" "_":"Huntington's disease CSF"} {"#name":"keyword" "$":{"id":"k0425"} "$$":[{"#name":"text" "_":"cerebrospinal fluid MPTP"} {"#name":"keyword" "$":{"id":"k0435"} "$$":[{"#name":"text" "_":"α-synuclein the 1-methyl-4-phenyl 1 2 3 6-tetrahydropyridine PBMCs"} {"#name":"keyword" "$":{"id":"k0445"} "$$":[{"#name":"text" "_":"peripheral blood mononuclear cells APCs"} {"#name":"keyword" "$":{"id":"k0455"} "$$":[{"#name":"text" "_":"antigen-presenting cells DMF"} {"#name":"keyword" "$":{"id":"k0465"} "$$":[{"#name":"text" "_":"dimethyl fumarate MCAO"} {"#name":"keyword" "$":{"id":"k0475"} "$$":[{"#name":"text" "_":"middle cerebral artery occlusion TLE"} {"#name":"keyword" "$":{"id":"k0485"} "$$":[{"#name":"text" "_":"temporal lobe epilepsy HMGB1"} {"#name":"keyword" "$":{"id":"k0495"} "$$":[{"#name":"text" "_":"high mobility group box-1 MDD"} {"#name":"keyword" "$":{"id":"k0505"} "$$":[{"#name":"text" "_":"major depressive disorder NSA"} {"#name":"keyword" "$":{"id":"k0515"} "$$":[{"#name":"text" "_":"necrosulfonamide MAF"} {"#name":"keyword" "$":{"id":"k0525"} "$$":[{"#name":"text" "_":"mafenide
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