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      Metaflammation: Tissue-Specific Alterations of the NLRP3 Inflammasome Platform in Metabolic Syndrome.

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          Abstract

          In the last decades, the extension of life expectancy and the increased consumption of foods rich in saturated fats and added sugars have exposed the general population to emerging health problems. The prevalence of metabolic syndrome (MS), composed of a cluster of factors as obesity, dyslipidemia, hyperglycemia, and hypertension, is rapidly increasing in industrialized and developing countries leading to precocious onset of age-related diseases. Indeed, oxidative stress, accumulation of advanced glycation endproducts, and a chronic low-grade inflammation are common features of MS and physiological ageing. In particular, the entire set of MS factors contributes to the development of an inflammatory status named metaflammation, which has been associated with activation of early innate immune response through the assembling of the multiprotein complex inflammasome. The most investigated family of inflammasome platforms is the NOD-like receptor pyridine containing (NLRP) 3, which is activated by several exogenous and endogenous stimuli, leading to the sequential cleavage of caspase-1 and IL-1β, followed by secretion of active IL-1β. We here collect the most recent findings on NLRP3 activation in MS providing evidence of its central role in disease progression and organ dysfunction in target tissues of metaflammation, in particular in cardiovascular, hepatic and renal complications, with a focus on oxidative stress and advanced glycation endproducts. A wide overview of the most promising strategies for the modulation of NLRP3 activation and related metabolic repercussions is also provided, since the finding of specific pharmacological tools is an urgent requirement to reduce the social and economic burden of MS- and elderly-associated diseases.

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          Author and article information

          Journal
          Curr. Med. Chem.
          Current medicinal chemistry
          Bentham Science Publishers Ltd.
          1875-533X
          0929-8673
          2018
          : 25
          : 11
          Affiliations
          [1 ] Department of Clinical and Biological Sciences, University of Turin, Torino, Italy.
          [2 ] Department of Life Sciences and Systems Biology, University of Turin, Torino, Italy.
          [3 ] Department of Drug Science and Technology, University of Turin, Torino, Italy.
          Article
          CMC-EPUB-82707
          10.2174/0929867324666170407123522
          28403789
          a4d9b689-40e4-44bd-a41b-0d9a96d74ccb
          History

          myocardial ischemia/reperfusion,Metabolic syndrome,NLRP3 inflammasome,aging,chronic kidney disease,metaflammation,oxidative stress,steatohepatitis.

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