References
[1]. Zhang, Y., Zhao, Y., Zhang, J. and Yang, G., "Mechanisms of NLRP3 Inflammasome Activation: Its Role in the Treatment of Alzheimer’s Disease", Neurochem. Res. 45, 2560–2572 (2020).
[2]. Coll, R. C. et al, "MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibition", Nat. Chem. Biol. 15, 556–559 (2019).
[3]. Stancu, I.-C. et al, "Aggregated Tau activates NLRP3–ASC inflammasome exacerbating exogenously seeded and non-exogenously seeded Tau pathology in vivo", Acta Neuropathol. (Berl.) 137, 599–617 (2019).
[4]. Qi, Y., Klyubin, I., Ondrejcak, T., Hu, N.-W. and Rowan, M. J., "Enduring glucocorticoid-evoked exacerbation of synaptic plasticity disruption in male rats modelling early Alzheimer’s disease amyloidosis," Neuropsychopharmacology 46, 2170–2179 (2021).
[5]. Jia, L. et al, " Inhibition of NLRP3 alleviated chemotherapy-induced cognitive impairment in rats," Neurosci. Lett. 793, 136975 (2023).
[6]. Lonnemann, N. et al, "The NLRP3 inflammasome inhibitor OLT1177 rescues cognitive impairment in a mouse model of Alzheimer’s disease", Proc. Natl. Acad. Sci. U. S. A. 117, 32145–32154 (2020).
[7]. Haneklaus, M. et al, "Cutting edge: miR-223 and EBV miR-BART15 regulate the NLRP3 inflammasome and IL-1β production," J. Immunol. Baltim. Md 1950 189, 3795–3799 (2012).
[8]. Campani, V. et al, "Hybrid lipid self-assembling nanoparticles for brain delivery of microRNA", Int. J. Pharm. 588, 119693 (2020).
[9]. Mancuso, R. et al, " Circulatory miR-223-3p Discriminates Between Parkinson's and Alzheimer's Patients", Sci Rep. 28, 9(1), 9393 (2019)
[10]. de Rivero Vaccari, J. P. et al, "Mechanism action of IC 100, a humanized IgG4 monoclonal antibody targeting apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC)", Transl Res. 251, 27–40 (2023).
[11]. Dick, M., Sborgi, L., Rühl, S., Hiller, S. and Broz, P, "ASC filament formation serves as a signal amplification mechanism for inflammasomes", Nat. Commun. 7, 11929 (2016).
[12]. Vontell, R. T. et al, "Identification of inflammasome signaling proteins in neurons and microglia in early and intermediate stages of Alzheimer’s disease", Brain Pathol. Zurich Switz. e13142 (2022).
[13]. Kang, J.-H. et al, "Novel Activity of ODZ10117, a STAT3 Inhibitor, for Regulation of NLRP3 Inflammasome Activation", Int. J. Mol. Sci. 24, 6079 (2023).
[14]. He, Y., Zeng, M. Y., Yang, D., Motro, B. and Núñez, G, "NEK7 is an essential mediator of NLRP3 activation downstream of potassium efflux", Nature 530, 354–357 (2016).
[15]. Jang, A.-R., Lee, H.-N., Hong, J. J., Kim, Y.-M. Park, J.-H., "Ethanol extract of Chrysanthemum zawadskii inhibits the NLRP3 inflammasome by suppressing ASC oligomerization in macrophages", Exp. Ther. Med. 25, 128 (2023).
[16]. Jayabalan, N. et al, "A Review of RRx-001: A Late-Stage Multi-Indication Inhibitor of NLRP3 Activation and Chronic Inflammation", Drugs 83, 389–402 (2023).
[17]. Reid, T., Oronsky, B., Caroen, S. and Cabrales, P., "The direct NLRP3 inhibitor and Phase 3 small molecule anticancer agent, RRx-001, protects aged triple transgenic Alzheimer’s disease model mice from CNS degeneration and cognitive decline", Alzheimers Dement. 18, e061516 (2022).
[18]. Youm, Y.-H. et al, "The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome–mediated inflammatory disease", Nat. Med. 21, 263–269 (2015).
[19]. Shippy, D.-C. et al, " β-Hydroxybutyrate inhibits inflammasome activation to attenuate Alzheimer’s disease pathology", J. Neuroinflammation 21;17(1):280 (2020)
[20]. Kuwar, R. et al, "A Novel Inhibitor Targeting NLRP3 Inflammasome Reduces Neuropathology and Improves Cognitive Function in Alzheimer’s Disease Transgenic Mice", J. Alzheimers Dis. 82, 1769–1783 (2021).
[21]. Zhang, C. et al, "Targeting NLRP3 signaling by a novel-designed sulfonylurea compound for inhibition of microglial inflammation", Bioorg. Med. Chem. 58, 116645 (2022).
[22]. Wang, B. et al, "Structural Proteomic Profiling of Cerebrospinal Fluids to Reveal Novel Conformational Biomarkers for Alzheimer’s Disease", J. Am. Soc. Mass Spectrom. 34, 459–471 (2023).
[23]. Mu, X. et al, "A novel label-free universal biosensing platform based on CRISPR/Cas12a for biomarker detection", Talanta 251, 123795 (2023).
Cite this article
Yan,Z. (2023). The application of NLRP3 inflammasome inhibition in Alzheimer’s disease therapeutics: Clinical benefits, applications, current limitations, and future development. Theoretical and Natural Science,20,273-280.
Data availability
The datasets used and/or analyzed during the current study will be available from the authors upon reasonable request.
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References
[1]. Zhang, Y., Zhao, Y., Zhang, J. and Yang, G., "Mechanisms of NLRP3 Inflammasome Activation: Its Role in the Treatment of Alzheimer’s Disease", Neurochem. Res. 45, 2560–2572 (2020).
[2]. Coll, R. C. et al, "MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibition", Nat. Chem. Biol. 15, 556–559 (2019).
[3]. Stancu, I.-C. et al, "Aggregated Tau activates NLRP3–ASC inflammasome exacerbating exogenously seeded and non-exogenously seeded Tau pathology in vivo", Acta Neuropathol. (Berl.) 137, 599–617 (2019).
[4]. Qi, Y., Klyubin, I., Ondrejcak, T., Hu, N.-W. and Rowan, M. J., "Enduring glucocorticoid-evoked exacerbation of synaptic plasticity disruption in male rats modelling early Alzheimer’s disease amyloidosis," Neuropsychopharmacology 46, 2170–2179 (2021).
[5]. Jia, L. et al, " Inhibition of NLRP3 alleviated chemotherapy-induced cognitive impairment in rats," Neurosci. Lett. 793, 136975 (2023).
[6]. Lonnemann, N. et al, "The NLRP3 inflammasome inhibitor OLT1177 rescues cognitive impairment in a mouse model of Alzheimer’s disease", Proc. Natl. Acad. Sci. U. S. A. 117, 32145–32154 (2020).
[7]. Haneklaus, M. et al, "Cutting edge: miR-223 and EBV miR-BART15 regulate the NLRP3 inflammasome and IL-1β production," J. Immunol. Baltim. Md 1950 189, 3795–3799 (2012).
[8]. Campani, V. et al, "Hybrid lipid self-assembling nanoparticles for brain delivery of microRNA", Int. J. Pharm. 588, 119693 (2020).
[9]. Mancuso, R. et al, " Circulatory miR-223-3p Discriminates Between Parkinson's and Alzheimer's Patients", Sci Rep. 28, 9(1), 9393 (2019)
[10]. de Rivero Vaccari, J. P. et al, "Mechanism action of IC 100, a humanized IgG4 monoclonal antibody targeting apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC)", Transl Res. 251, 27–40 (2023).
[11]. Dick, M., Sborgi, L., Rühl, S., Hiller, S. and Broz, P, "ASC filament formation serves as a signal amplification mechanism for inflammasomes", Nat. Commun. 7, 11929 (2016).
[12]. Vontell, R. T. et al, "Identification of inflammasome signaling proteins in neurons and microglia in early and intermediate stages of Alzheimer’s disease", Brain Pathol. Zurich Switz. e13142 (2022).
[13]. Kang, J.-H. et al, "Novel Activity of ODZ10117, a STAT3 Inhibitor, for Regulation of NLRP3 Inflammasome Activation", Int. J. Mol. Sci. 24, 6079 (2023).
[14]. He, Y., Zeng, M. Y., Yang, D., Motro, B. and Núñez, G, "NEK7 is an essential mediator of NLRP3 activation downstream of potassium efflux", Nature 530, 354–357 (2016).
[15]. Jang, A.-R., Lee, H.-N., Hong, J. J., Kim, Y.-M. Park, J.-H., "Ethanol extract of Chrysanthemum zawadskii inhibits the NLRP3 inflammasome by suppressing ASC oligomerization in macrophages", Exp. Ther. Med. 25, 128 (2023).
[16]. Jayabalan, N. et al, "A Review of RRx-001: A Late-Stage Multi-Indication Inhibitor of NLRP3 Activation and Chronic Inflammation", Drugs 83, 389–402 (2023).
[17]. Reid, T., Oronsky, B., Caroen, S. and Cabrales, P., "The direct NLRP3 inhibitor and Phase 3 small molecule anticancer agent, RRx-001, protects aged triple transgenic Alzheimer’s disease model mice from CNS degeneration and cognitive decline", Alzheimers Dement. 18, e061516 (2022).
[18]. Youm, Y.-H. et al, "The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome–mediated inflammatory disease", Nat. Med. 21, 263–269 (2015).
[19]. Shippy, D.-C. et al, " β-Hydroxybutyrate inhibits inflammasome activation to attenuate Alzheimer’s disease pathology", J. Neuroinflammation 21;17(1):280 (2020)
[20]. Kuwar, R. et al, "A Novel Inhibitor Targeting NLRP3 Inflammasome Reduces Neuropathology and Improves Cognitive Function in Alzheimer’s Disease Transgenic Mice", J. Alzheimers Dis. 82, 1769–1783 (2021).
[21]. Zhang, C. et al, "Targeting NLRP3 signaling by a novel-designed sulfonylurea compound for inhibition of microglial inflammation", Bioorg. Med. Chem. 58, 116645 (2022).
[22]. Wang, B. et al, "Structural Proteomic Profiling of Cerebrospinal Fluids to Reveal Novel Conformational Biomarkers for Alzheimer’s Disease", J. Am. Soc. Mass Spectrom. 34, 459–471 (2023).
[23]. Mu, X. et al, "A novel label-free universal biosensing platform based on CRISPR/Cas12a for biomarker detection", Talanta 251, 123795 (2023).