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Hereto, there is an urgent unmet need to develop mechanistic treatments directed at root causes of AF. Recent research findings indicate a key role for inflammasomes and derailed proteostasis as root causes of AF. Here, we elaborate on the molecular mechanisms of these 2 emerging key pathways driving the pathogenesis of AF. First the role of NLRP3 (NACHT, LRR, and PYD domains-containing protein 3) inflammasome on AF pathogenesis and cardiomyocyte remodeling is discussed. Then we highlight pathways of proteostasis derailment, including exhaustion of cardioprotective heat shock proteins, disruption of cytoskeletal proteins via histone deacetylases, and the recently discovered DNA damage-induced nicotinamide adenine dinucleotide\n            <jats:sup>+<\/jats:sup>\n            depletion to underlie AF. Moreover, potential interactions between the inflammasomes and proteostasis pathways are discussed and possible therapeutic targets within these pathways indicated.\n          <\/jats:p>","DOI":"10.1161\/circresaha.119.316364","type":"journal-article","created":{"date-parts":[[2020,6,18]],"date-time":"2020-06-18T18:00:46Z","timestamp":1592503246000},"page":"73-90","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":91,"title":["Inflammasomes and Proteostasis Novel Molecular Mechanisms Associated With Atrial Fibrillation"],"prefix":"10.1161","volume":"127","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4768-234X","authenticated-orcid":false,"given":"Na","family":"Li","sequence":"first","affiliation":[{"name":"From the Department of Medicine (Cardiovascular Research) (N.L.), Baylor College of Medicine, Houston, TX"},{"name":"Department of Molecular Physiology and Biophysics (N.L.), Baylor College of Medicine, Houston, 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