Abstract
Neuroinflammatory response is the immune response mechanism of the innate immune system of the central nervous system. Both primary and secondary injury can activate neuroinflammatory response. Among them, the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome plays a key role in the inflammatory response of the central system. Inflammasome is a type of pattern recognition receptor, a cytoplasmic polyprotein complex composed of members of the Nod-like receptor (NLR) family and members of the pyrin and HIN domain (PYHIN) family, which can be affected by a variety of pathogen-related molecular patterns or damage-related molecular patterns are activated. As one of the research hotspots in the field of medical research in recent years, there are increasing researches on immune function abnormalities in the onset of neurological diseases such as depression, AD, ischemic brain injury and cerebral infarction, the NLRP3 inflammasome causes the activated caspase-1 to cleave pre-interleukin-1β and pre-interleukin-18 into mature interleukin-1β and interleukin-18, in turn, a large number of inflammatory factors are produced, which participate in the occurrence and development of the above-mentioned diseases. Targeted inhibition of the activation of inflammasomes can reduce the inflammatory response, promote the survival of nerve cells, and achieve neuroprotective effects. This article reviews NLRP3 inflammasome’s role in neurological diseases and related regulatory mechanisms, which providing references for future research in this field.
Highlights
A growing body of evidence has shown that inflammation plays a crucial role in the occurrence and development of various nervous system diseases
When there is a high concentration of K+ outside the cell, the interaction between Nek7 and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) is inhibited, indicating that this interaction requires the outflow of K+, it is considered that the decrease in K+ concentration in the cell causes the conformational change of NLRP3, which promotes the binding of Nek7 to NLRP3; when NLRP3 has an activating mutation that does not depend on K+ efflux (NLRP3R258W), the activation of inflammasomes still requires Nek7 (He et al, 2016b)
NLRP3 inflammasome is a multi-molecular complex in the cytoplasm that controls the processing of caspase-1 and the maturation of pro-inflammatory cytokines, as the most studied inflammasome, it is closely related to a variety of inflammatory diseases and plays an important role in stimulating and regulating innate immunity and inflammatory response
Summary
A growing body of evidence has shown that inflammation plays a crucial role in the occurrence and development of various nervous system diseases. When NLRP3 recognizes pathogens and intracellular danger signals, it undergoes oligomerization, binding to the adaptor protein ASC and recruiting caspase-1 precursors These form the aggregates of the NLRP3 inflammasome. The classical activation of the NLRP3 inflammatory complex generally requires two steps, including the preexcitation of NLRP3 inflammasome and activation of NLRP3 inflammasome (Liu et al, 2016a): 1) Initiation signal: NLRP3 is stimulated by the danger signal to initiate the transcription and expression of pro-IL-1β and NLRP3 and other precursor proteins through the nuclear factor κB pathway (Luo et al, 2014); 2) Activation signal: It is mainly the assembly of NLRP3 inflammasome and the process by which activated caspase-1 processes and modifies downstream inflammatory factors and leads to their mature secretion (Hoyt et al, 2017; Próchnicki and Latz, 2017). Further in vitro experiments are needed to study the molecular mechanism of the interaction between caspase 1 and caspase 11 and the mechanism of caspase 11 activation of non-classical pathways or indirect activation of the classic NLRP3 inflammasome pathway
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
