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The role of NLRP6 in the development and progression of neurological diseases

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Abstract

The nervous system possesses the remarkable ability to undergo changes in order to store information; however, it is also susceptible to damage caused by invading pathogens or neurodegenerative processes. As a member of nucleotide-binding oligomerization domain-like receptor (NLR) family, the NLRP6 inflammasome serves as a cytoplasmic innate immune sensor responsible for detecting microbe-associated molecular patterns. Upon activation, NLRP6 can recruit the adapter protein apoptosis-associated speck-like protein (ASC) and the inflammatory factors caspase-1 or caspase-11. Consequently, inflammasomes are formed, facilitating the maturation and secretion of pro-inflammatory cytokines such as inflammatory factors-18 (IL-18) and inflammatory factors-1β (IL-1β). Precise regulation of NLRP6 is crucial for maintaining tissue homeostasis, as dysregulated inflammasome activation can contribute to the development of various diseases. Furthermore, NLRP6 may also play a role in the regulation of extraintestinal diseases. In cells of the brain, such as astrocytes and neurons, NLRP6 inflammasome are also present. Here, the assembly and subsequent activation of caspase-1 mediated by NLRP6 contribute to disease progression. This review aims to discuss the structure and function of NLRP6, explain clearly the mechanisms that induce and activate NLRP6, and explore its role within the central and peripheral nervous system.

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Funding

This study was supported by grants from the National Natural Science Foundation of China (81871019, 81671286) and Graduate Research Innovation Project of Chongqing (CYS23322).

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Authors and Affiliations

  1. Institute of Neuroscience, Chongqing Medical University, No. 1, Yixuayuan Road, Yuzhong District, Chongqing, 400016, China

    Yiming Guo, Jiaqi Song, Mengyu Yan, Yingxi Chen, Lihong Huang, Yurou He & Weihua Yu

  2. Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China

    Jiarui Liu & Yang Lü

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  1. Yiming Guo
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  2. Jiaqi Song
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  3. Mengyu Yan
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  4. Yingxi Chen
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  5. Lihong Huang
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  9. Weihua Yu
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Contributions

YM. wrote the main manuscript text; JQ. and MY. checked the draft; YX and LH made the data curation; JR and YR collected the information. All authors reviewed the manuscript.

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Correspondence to Weihua Yu.

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Guo, Y., Song, J., Yan, M. et al. The role of NLRP6 in the development and progression of neurological diseases. Mol Biol Rep 51, 351 (2024). https://doi.org/10.1007/s11033-024-09293-z

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