Targeting NLRP3 Inflammasome in the Treatment of CNS Diseases

Abstract

Central nervous system (CNS) is one of the largest killers of people’s health all over the world. The overactivation of the immune and inflammatory responses is considered as an important factor, contributing to the pathogenesis and progression of CNS disorders. Among all kinds of immune and inflammatory reaction, the inflammasome, a complex of proteins, has been drawn increasingly attention to by researchers. The initiation and activation of the inflammasome is involved in the onset of various kinds of diseases. The NLRP3 inflammasome, the most studied member of the inflammasome, is closely associated with many kinds of CNS disorders. Here in this review, the roles of the NLRP3 inflammasome in the pathogenesis and progression of several well-known CNS diseases would be discussed, including cerebrovascular diseases, neurodegenerative diseases, multiple sclerosis, depression as well as other CNS disorders. In addition, several therapeutic strategies targeting on the NLRP3 inflammasome for the treatment of CNS disorders would be described in this review.

The Role of Mitochondria in Inflammation: From Cancer to Neurodegenerative Disorders

“…Another therapeutic approach to reduce neuroinflammation is blocking necroptotic pathways with synthetic inhibitors (RIP1 inhibitors, RIP3 inhibitors, MLKL inhibitors) to mitigate NDD progression [114]. Drug treatments aimed at manipulating inflammasome assembly therapeutically are currently used in clinic [115], but, despite their promising efficacy, they still do not resolve the disease. The low efficacy of actual therapies in treating NDDs might be due to the complexity of neurodegenerative processes, which involve neuroinflammation but also have roots in genetic predisposition and environmental factors.…”

São Paulo School of Advanced Sciences on Vaccines: an overview

“…Similar data were also demonstrated for Legionella pneumophila [8]. Inflammasome components can be also expressed by cells of the nervous system, and eventually prompt neurological processes [9]. Hence, Dr. Dario Zamboni (University of São Paulo, Brazil) discussed how the innate immune system discriminates between pathogenic and non-pathogenic microbes.…”

Update of inflammasome activation in microglia/macrophage in aging and aging‐related disease

“…As that in acute ischemic stroke, inflammasome products exacerbate BBB injury and promote leukocyte recruitment, thus enlarging perihematomal edema and exacerbating brain injury . Targeting NLRP3 inflammasome activation may be a promising therapeutic strategy for ICH . The P 2 X 7 receptor is upstream of NLRP3 activation, and its inhibition has a pronounced neuroprotective effect in an ICH rat model .…”

“…76,79 Targeting NLRP3 inflammasome activation may be a promising therapeutic strategy for ICH. 80,81 The P 2 X 7 receptor is upstream of NLRP3 activation, and its inhibition has a pronounced neuroprotective effect in an ICH rat model. 80 Blocking Caspase-1 signaling or NLRP3 inflammasome has been demonstrated to effectively reduce the inflammatory responses and improved disease outcomes in ICH.…”