Molecular Regulation of Cell Fate in Cerebral Ischemia: Role of the Inflammasome and Connected Pathways

Abstract

Analogous to Toll-like receptors, NOD-like receptors represent a class of pattern recognition receptors, which are cytosolic and constitute part of different inflammasomes. These large protein complexes are activated not only by different pathogens, but also by sterile inflammation or by specific metabolic conditions. Mutations can cause hereditary autoinflammatory systemic diseases, and inflammasome activation has been linked to many multifactorial diseases, such as diabetes or cardiovascular diseases. Increasing data also support an important role in different central nervous diseases such as stroke. Thus, the current knowledge of the functional role of this intracellular 'master switch' of inflammation is discussed with a focus on its role in ischemic stroke, neurodegeneration, and also with regard to the recent data which argues for a relevant role in other organs or biologic systems which influence stroke incidence or prognosis.

Poststroke Inflammasome Expression and Regulation in the Peri-Infarct Area by Gonadal Steroids after Transient Focal Ischemia in the Rat Brain

“…The knowledge about inflammasome activation during ischemic stroke is sketchy, and only in the past years were distinct inflammasome complexes discovered as mediators of inflammatory mechanism leading to cell death in ischemic stroke [10,43,44]. A recently published review article by Trendelenburg [45] focuses on the importance of inflammatory processes during severe ischemic stroke conditions and gives a state-of-the-art overview about the current knowledge. Not only the DAMP pattern recognition receptor interaction and classical two-step model of inflammasome activation is highlighted during acute ischemia, but also the critical role of the complement system.…”

“…This would explain steroid effects. And finally, since NLRP1 and NLRP3 signaling converges to Casp1 activation [10,44,45] and they show a different cellular allocation, our Western blot analysis might mix up different reactions and only give a summation of effects rather than individual responses.…”

Minocycline Suppresses NLRP3 Inflammasome Activation in Experimental Ischemic Stroke

“…Increasing evidence support that multiprotein complexes known as inflammasomes contribute significantly to ischemic brain injury following stroke [4,5] . The NOD (nucleotide-binding oligomerization domain)-like receptor (NLR) pyrin-domain-containing 3 (NLRP3) inflammasomes are abundantly expressed in the brain and immune cells.…”

Inflammasomes are neuroprotective targets for sex steroids

“…Besides being part of the anti-viral and anti-bacterial infection cascade, an emerging body of literature point to inflammasomes also to be involved in the pathogenesis of classical neurodegenerative diseases, i.e., Alzheime rs disease and Parkinson syndrome diseases, acute traumatic events including stroke, and even psychiatric illness such as major depressive disorders [1,[3][4][5][6]. The importance and unique feature of inflammasomes at the beginning and during the flowchart of inflammation makes them ideal candidates as points of therapeutic applications.…”