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. 2020 Jul;15(7):1249-1250.
doi: 10.4103/1673-5374.272576.

Role of the NLRP3 inflammasome in neurodegenerative diseases and therapeutic implications

Yanhui Duan  1 , Nathan Kelley  1 , Yuan He  1
Affiliations

Role of the NLRP3 inflammasome in neurodegenerative diseases and therapeutic implications

Yanhui Duan et al. Neural Regen Res. 2020 Jul.
No abstract available

PubMed Disclaimer

Conflict of interest statement

None

Figures

Figure 1
Figure 1
Role of NLRP3 inflammasome in neurodegenerative diseases. Cytokines, pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs) engage their receptors, leading to activation of transcription factor nuclear factor-κB (NF-κB) and subsequent upregulation of NLR family pyrin domain containing 3 protein (NLRP3) and pro-IL-1β (Signal 1). Phagocytosis of misfolded amyloid-β (Aβ) or α-synuclein (α-Syn) induces lysosomal damage and subsequent release of cathepsin B and ROS accumulation, which trigger NLRP3 inflammasome assembly and caspase1 activation (Signal 2). Activated caspase1 cleaves pro-IL-1β, pro-IL-18 and gasdermin D (GSDMD) into their bioactive forms. Mitochondrial dysfunction, K+ efflux, or both might also contribute to NLRP3 inflammasome activation by Aβ or α-Syn. Proinflammatory cytokines, such as IL-1β and IL-18, or other inflammatory mediators induce neuronal damage and death, leading to neurodegenerative diseases. AD: Alzheimer’s disease; IL: interleukin; NLRP3: NLR family pyrin domain containing 3 protein; PD: Parkinson’s disease; ROS: reactive oxygen species; TLR: Toll-like receptor.
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References

    1. Broz P, Dixit VM. Inflammasomes: mechanism of assembly, regulation and signalling. Nat Rev Immunol. 2016;16:407–420. - PubMed
    1. Codolo G, Plotegher N, Pozzobon T, Brucale M, Tessari I, Bubacco L, de Bernard M. Triggering of inflammasome by aggregated alpha-synuclein, an inflammatory response in synucleinopathies. PLoS One. 2013;8:e55375. - PMC - PubMed
    1. Dempsey C, Rubio Araiz A, Bryson KJ, Finucane O, Larkin C, Mills EL, Robertson AAB, Cooper MA, O’Neill LAJ, Lynch MA. Inhibiting the NLRP3 inflammasome with MCC950 promotes non-phlogistic clearance of amyloid-beta and cognitive function in APP/PS1 mice. Brain Behav Immun. 2017;61:306–316. - PubMed
    1. Dinarello CA, Simon A, van der Meer JW. Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases. Nat Rev Drug Discov. 2012;11:633–652. - PMC - PubMed
    1. Halle A, Hornung V, Petzold GC, Stewart CR, Monks BG, Reinheckel T, Fitzgerald KA, Latz E, Moore KJ, Golenbock DT. The NALP3 inflammasome is involved in the innate immune response to amyloid-beta. Nat Immunol. 2008;9:857–865. - PMC - PubMed