Cited by 469Inflammasome and immune disordersNeuroinflammation and Neurodegeneration MechanismsImmune Response and Inflammation

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NLRP3 Inflammasome in Neurological Diseases, from Functions to Therapies

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Song, Limin, Pei, Lei, Yao, Shanglong, Wu, Yan, Shang, You·2017·Frontiers in Cellular Neuroscience

DOI 10.3389/fncel.2017.00063PMC PMC5343070

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Abstract

Neuroinflammation has been identified as a causative factor of multiple neurological diseases. The nucleotide-binding oligomerization domain-, leucine-rich repeat- and pyrin domain-containing 3 (NLRP3) inflammasome, a subcellular multiprotein complex that is abundantly expressed in the central nervous system (CNS), can sense and be activated by a wide range of exogenous and endogenous stimuli such as microbes, aggregated and misfolded proteins, and adenosine triphosphate, which results in activation of caspase-1. Activated caspase-1 subsequently leads to the processing of interleukin-1β (IL-1β) and interleukin-18 (IL-18) pro-inflammatory cytokines and mediates rapid cell death. IL-1β and IL-18 drive inflammatory responses through diverse downstream signaling pathways, leading to neuronal damage. Thus, the NLRP3 inflammasome is considered a key contributor to the development of neuroinflammation. In this review article, we briefly discuss the structure and activation the NLRP3 inflammasome and address the involvement of the NLRP3 inflammasome in several neurological disorders, such as brain infection, acute brain injury and neurodegenerative diseases. In addition, we review a series of promising therapeutic approaches that target the NLRP3 inflammasome signaling including anti-IL-1 therapy, small molecule NLRP3 inhibitors and other compounds, however, these approaches are still experimental in neurological diseases. At present, it is plausible to generate cell-specific conditional NLRP3 knockout (KO) mice via the Cre system to investigate the role of the NLRP3 inflammasome, which may be instrumental in the development of novel pharmacologic investigations for neuroinflammation-associated diseases.

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Authors: Song, L., Pei, L., Yao, S., Wu, Y., & Shang, Y.
Affiliations: Wuhan Union Hospital (CN)
Huazhong University of Science and Technology (CN)
Corresponding author: Wu, Yan
Shang, You
ORCID: Song, Limin
Pei, Lei
Yao, Shanglong
Wu, Yan
Shang, You
Venue: Frontiers in Cellular Neuroscience
Publisher: Frontiers Media SA
Published: 2017-03-09
Volume: 11
Pages: 63-63
ISSN: 1662-5102 (ISSN-L)
DOI: 10.3389/fncel.2017.00063
PMC: PMC5343070
OpenAlex: W2591960163
Cited by: 467
References: 255
Citations by year: 2026: 29 · 2025: 42 · 2024: 52 · 2023: 66 · 2022: 60 · 2021: 74 · 2020: 51 · 2019: 41 · 2018: 35 · 2017: 13
FWCI: 3.58
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Natural Science Foundation of China (81270018, 81471202, 81271270)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords: NLRP3 inflammasome, neuroinflammation, neurological disorders, caspase-1, IL-1β, IL-18, neurodegenerative diseases, brain infection, acute brain injury, NLRP3 inhibitors, anti-IL-1 therapy, conditional knockout mice

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NLRP3 Inflammasome in Neurological Diseases, from Functions to Therapies

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