2021
DOI: 10.1002/ana.26158
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Targeting Inflammasomes to Treat Neurological Diseases

Abstract: Inflammasomes are multimeric protein complexes that can sense a plethora of microbe‐ and damage‐associated molecular signals. They play important roles in innate immunity and are key regulators of inflammation in health and disease. Inflammasome‐mediated processing and secretion of proinflammatory cytokines such as interleukin (IL) 1β and IL‐18 and induction of pyroptosis, a proinflammatory form of cell death, have been associated with the development and progression of common immune‐mediated and degenerative … Show more

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Cited by 62 publications
(41 citation statements)
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“…Besides monocytes and macrophages, the NLRP3 inflammasome can also be activated in a wide range of endothelial, epithelial, and mesenchymal cells, thus, related to various inflammatory diseases in different organs such as the skin, brain, and liver. Thus, the NLRP3 inflammasome has been implicated in central nervous system (CNS) diseases, such as multiple sclerosis (MS), Alzheimer’s disease (AD), and Parkinson’s disease (PD) [ 185 , 186 ], metabolic diseases including non-alcoholic fatty liver disease (NAFLD), gout, type 2 diabetes, and obesity-induced insulin resistance [ 187 ], cardiovascular diseases (CVDs) [ 17 , 188 ], and rheumatoid arthritis (RA) [ 189 ] ( Figure 4 ). Moreover, the increased IL-1β and ASC expression can be detected in the colon of patients with inflammatory bowel diseases (IBDs) [ 190 ], while systemic lupus erythematosus (SLE) patients exhibit an increased level of NLRP3 proteins in macrophages and tissues [ 191 , 192 ].…”
Section: Roles Of Inflammasomes In Diseasesmentioning
confidence: 99%
“…Besides monocytes and macrophages, the NLRP3 inflammasome can also be activated in a wide range of endothelial, epithelial, and mesenchymal cells, thus, related to various inflammatory diseases in different organs such as the skin, brain, and liver. Thus, the NLRP3 inflammasome has been implicated in central nervous system (CNS) diseases, such as multiple sclerosis (MS), Alzheimer’s disease (AD), and Parkinson’s disease (PD) [ 185 , 186 ], metabolic diseases including non-alcoholic fatty liver disease (NAFLD), gout, type 2 diabetes, and obesity-induced insulin resistance [ 187 ], cardiovascular diseases (CVDs) [ 17 , 188 ], and rheumatoid arthritis (RA) [ 189 ] ( Figure 4 ). Moreover, the increased IL-1β and ASC expression can be detected in the colon of patients with inflammatory bowel diseases (IBDs) [ 190 ], while systemic lupus erythematosus (SLE) patients exhibit an increased level of NLRP3 proteins in macrophages and tissues [ 191 , 192 ].…”
Section: Roles Of Inflammasomes In Diseasesmentioning
confidence: 99%
“…SIRT2 was found to be specifically upregulated in cognitively unaffected ALS patients within corresponding brain regions to NLRP3 , and they thereby proposed its elevated expression to be a marker of cognitive resilience in ALS pathogenesis. The study adds to previous research suggesting that inappropriate activation of the inflammasome plays a role in neurodegenerative conditions, including ALS, and highlights that modulation of the inflammasome could be a therapeutic target in people with ALS, particularly in those with cognitive symptoms [13–16].…”
Section: Figurementioning
confidence: 66%
“…Further demonstration of the enhanced inflammatory signature of PPMS OLs in basal conditions is their strong upregulation of the inflammasome gene Nlrp2 , confirmed at the protein level in both PPMS OLs and OLs in the NAWM of post-mortem MS tissues. Inflammasomes, particularly NLRP3, have been implicated in MS pathophysiology and are considered promising therapeutic targets and biomarkers, especially for PPMS ( Boziki et al, 2020 ; Govindarajan et al, 2020 ; Malhotra et al, 2020 ; Lunemann et al, 2021 ). To this end, in our own work in the experimental autoimmune encephalomyelitis (EAE) model of MS, we showed that pan-inflammasome inhibition with a novel monoclonal antibody against the inflammasome adaptor protein ASC improved the clinical outcome ( Desu et al, 2020 ).…”
Section: Discussionmentioning
confidence: 99%