PD: Parkinson’s Disease; NLRP3: Nucleotide-binding domain-like Receptor Protein-3; LncZFAS1: Long-noncoding RNA ZFAS1; 6-OHDA: 6-hydroxydopamine; MPTP: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Ca2+: Calcium ion flux; TXNIP: Thioredoxin- Interacting Protein; TRX: Thioredoxin; ZFAS1: ZNFX1 Antisense RNA 1; ZNFX1: Zinc-finger structure, NFX1; miRNAs: MicroRNAs

Recently researchers have focused on the role of neuroinflammation in neurodegenerative diseases such as Alzheimer’s disease [1], atrophic lateral sclerosis [2], Huntington’s disease [3], Multiple sclerosis [4] and Parkinson’s disease (PD) [5]. PD is one of the leading neurodegenerative diseases in developed countries and the complete etiological scenario remains unknown. A-synuclein misfolding and aggregation, mitochondrial dysfunction, dysfunctional protein clearance and ubiquitin/proteasome systems, and neuroinflammation have been associated with PD. Harnessing inflammatory responses through targeted modulation of innate and adaptive immune responses has gained increasing interest in recent years as a potential therapeutic strategy. One of our articles, “A Novel Long-Noncoding RNA LncZFAS1 Prevents MPP+-Induced Neuroinflammation Through MIB1 Activation,” was studied on this topic and published online in Molecular Neurobiology in December, 2021 [6]. We explored the interaction of the LncZFAS1 and miR590-3p/TXNIP/MIB1 E3 ubiquitin ligase/NLRP3 pathway in the inflammation of PD. TXNIP ubiquitination via MIB1 E3 ubiquitin ligase regulates NLRP3 inflammasome activation in SH-SY5Y cells. In contrast, MPTP activated NLPR3 inflammasome through miR590-3p upregulation and directly interfered with MIB1-dependent TXNIP ubiquitination. LncZFAS1 overexpression inhibits this entire pathway through direct interference with miR590-3p, suggesting a novel research idea in mechanism of PD [6].

An appropriate model is the first and most important step in experimental neuropathological studies of PD. There is a clear criterion for PD model selection, but it needs to be further discussed in a PD non-neuroinflammatory study. The PD model includes toxin-based, gene-based, and synucleinbased models [7-11]. The toxin model imitates dopaminergic neurodegeneration by injecting neurotoxins, studying oxidative stress, mitochondrial respiratory defects, and abnormal protein aggregation among the three potentially important roles in PD pathogenesis [12,13]. The injected toxins include 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine (MPTP), paraquat, rotenone, and so on [14,15]. Rotenone and MPTP show little difference in their ability to use and inhibit the respiratory chain in animals [16]. However, only MPTP has a clear association with the onset of human PD; in other words, human exposure to MPTP results in a syndrome similar to the core neurological symptoms of PD and relatively selective dopaminergic neurodegeneration [17]. In addition, animal models based on modification of the gene or synaptic nuclear protein, including mice, rats, and fruit flies, cannot obtain stable dopaminergic nerve cell degeneration (i.e., cell death). Instead, they present a variety of neuropathological changes, including neuronal atrophy, malnutrition of neurites, and astrocytic proliferation with α-synaptic nuclear protein-positive LB-like inclusions [18]. Nevertheless, dopaminergic cell neurodegeneration changes are consistent in these models; α-synaptic nuclear proteins in the neurotoxin model represented by MPTP demonstrate a higher fitting degree of human PD [19,20]. The misfolding of proteins and dysfunction of the ubiquitinproteasome pathway, leading to the production of α-synaptic nuclear proteins, is critical to the pathogenesis of PD [21,22]. Neurotoxin-based models (particularly MPTP models) are important for elucidating the molecular cascade of cell death in dopaminergic neurons. Our study explored the TXNIP/MIB1 E3 ubiquitin ligase/NLRP3 pathway as one of the ubiquitinproteasome pathways; therefore, the adopted SH-SY5Y cell model (MPTP-induced) is appropriate. Gene expression is intact in the SH-SY5Y genome of major PD pathways, such as ROS metabolic columns, ubiquitin-proteasome system, dopamine metabolism, calcium signaling, mitochondria, and glycolysis [23]. Retinoic acid is often used to make SH-SY5Y cells morphologically similar to mature primary neurons and present a dopaminergic phenotype in PD [24-26]. Furthermore, SH-SY5Y cells have the advantages of highthroughput screening capacity of high proliferation cell lines, availability of clonal cells, and avoidance of ethical problems caused by human primary neural cell culture [27].

Neuroinflammation-mediated pyroptosis in PD neurological cells has been extensively studied [8,29,30]. Pyroptosis of NLRP3 activation in primary microglial cells is the core of PD progression in an MPTP-induced mouse model [31-35]. NLRP3 is an inflammatory complex mainly present in microglia and contains a caspase activation recruitment domain and caspase-1, which promotes the secretion of IL-1/ IL-18 and induces pyroptosis to destroy microglia to further release IL-1 [36-38]. Our results showed that SH-SY5Y cells generated and activated NLRP3 to induce cellular pyroptosis [6], revealing the role of NLRP3 and cells other than microglia in the neuroinflammatory response in PD. Besides, NLRP3 inflammasome activation may aggravate dopaminergic neuronal loss in Parkinson’s disease [39]. There is a link between the aggregation of α-synuclein, increased mitochondrial ROS, and cathepsin B release with the activation of microglial NLRP3 inflammation-mediated pyroptotic cell death of dopaminergic neurons in the substantia nigra[40]. Mitochondrial generation of ROS, mitophagy, loss of function of dopaminergic receptors, and lncRNA, are frequently connect with microglial NLRP3 inflammasome activation [41]. Activators with different biological activities and molecular structures can activate NLRP3, indicating that NLRP3 is activated by common cellular events rather than by physical interactions [42-46]. Common activators induce cell stress, and NLRP3 senses these cell pressures. However, it remains unclear how NLRP3 senses cell stress and which pathways induce climax in the process of NLRP3 activation and inflammatory body formation [47,48]. Multiple upstream signals are involved in these processes, including K⁺ or Cl^- efflux [49], calcium ion flux (Ca²⁺) [50], lysosomal destruction [51], mitochondrial dysfunction [52], metabolic changes [53] and trans-Golgi disassembly [54]. Thioredoxin-interacting protein (TXNIP), an endogenous inhibitor of the thioredoxin (TRX) system, is associated with importin-α, Jab1, E3 ubiquitin ligase ITCH, Mybbp1a, and NLRP3 [55]. TXNIP expression was increased and TXNIP knockdown by siRNA weakened the NLRP3 inflammasome activation response in αSynagg-stimulated mouse microglial cells, suggesting that TXNIP plays a nodal role in PD inflammation [56]. A TXNIP centered inflammasome regulation mechanism has not yet been reported. In our study, NLPR3 activation, ASC recruitment, caspase-1 cleavage, and IL-1 release were found to be dependent on TXNIP/TRX1 interaction. Increased TXNIP ubiquitination by MIB1 E3 ubiquitin ligase can regulate NLRP3 inflammasome activation in SH-SY5Y cell [6]. In the above chapter, we mention innate immunity and adaptive immunity. Microglia, the core of the innate immune network, secrete both anti- and proinflammatory cytokines and chemokines together with other factors that regulate not only adaptive immunity, but also neural function and neural homeostasis [28]. In PD, a- synuclein is associated with activated microglia and dopaminergic neuronal death. During disease, dopaminergic neurons accumulate α-synuclein together with other misfolded proteins (intracellular Lewy body). On injury or death, neurons release these proteins to the surrounding neuroenvironment and the modified proteins find their way to the peripheral lymphatic system. In our study, SH-SY5Y cell model (MPTP-induced) was used to simulate the partial process of dopamine neurons immune injury. Microglia was not involved in this process, which show certain value to understand the role of other cells in innate and adaptive immune responses.

ZNFX1 antisense RNA 1 (ZFAS1) is transcribed from the antisense direction of the zinc-finger structure NFX1 (ZNFX1), located on chromosome 20q13 [29]. LncZFAS1 has 14 transcripts created through alternative splicing (http:// asia.ensembl.org/Homo_sapiens/Gene/Summary?g= ENSG00000177410; r = 20:49278178–49299600). NR_003604.3, NR_036658.2, NR_003606.3, NR_003605.2 and NR_036659.2 transcripts are 1008, 946, 860, 689 and 504 nucleotides length, respectively [57]. LncZFAS1 is considered as an oncogene in almost all types of cancers, and therefore it is possible to forecast the clinical outcome of patients with different neoplasms by using expression amounts of ZFAS1 [57]. What’s more, lncZFAS1 is involved in inflammatory response processes in a variety of diseases, such as rheumatoid arthritis [58], acute lung injury [59], sepsis [60] and atherosclerosis [61]. ZFAS1 silencing has decreased proliferation, inflammation, autophagy, and enhanced apoptosis via miR-2682–5p/ ADAMTS9 axis in fibroblast-like synoviocytes of rheumatoid arthritis patients [58]. ZFAS1 up-regulation has increased inflammatory responses and hindered cholesterol effluence through sponging miR-654–3p and increasing ADAM10 and RAB22A expressions in the cell line model of atherosclerosis [61]. Inhibition of lncRNA ZFAS1 expression promotes the recovery of neurological function in traumatic brain injury [62]. Silencing of lncRNA ZFAS1, activation of the PI3K/AKT pathway, and increased expression of miR-421 regulate apoptosis and autophagy in epilepsy-related hippocampal neurons [63]. High expression of lncRNA ZFAS1 is associated with low levels of CRP, TNF-α, IL-1, and IL-6 in acute stroke patients [64], possibly because lncRNA ZFAS1 reduces miR-582 expression and upregulates nitric oxide synthase 3 expression to reduce pro-inflammatory cytokine production, thereby reducing inflammation in patients with acute brain stroke [65]. The relationship between LncZFAS1 and the NLRP3 inflammasome requires further investigation. MicroRNAs (miRNAs) target immune transcripts to fine-tune gene expression and turn on negative feedback loops, which help limit co-stimulation, set precise cellular activation thresholds, curtail inflammation, and control lymphocyte growth [66,67]. In a sepsis model, LncZFAS1 aggravates sepsis-induced progression of cardiac insufficiency by targeting miR-590-3p/NLRP3-mediated autophagy and pyroptosis [68]. Thus, we hypothesized that LncZFAS1 might regulate inflammasome activation and pyroptosis during Parkinson’s disease. E3 ubiquitin ligases act as the effectors of ubiquitination, a posttranslational modification characterized by the attachment of ubiquitin to a target protein. Modification cause protein rapid degradation by the proteasome or altering its localization or binding partners. As a member of the RING family of E3 ligases, MIB1 plays an important role in various biological processes by mediating the degradation of the different substrates. At the N terminus of MIB1 are two substratebinding domains termed MZM (Mib-Herc2/ZZ Zinc Finger/ Mib-Herc2) and REP (consisting of two Mib-repeat domains) that are cumulatively designated the “MIB” domain and which serve as the primary determinants of target specificity. These domains then connect via a series of ankyrin repeats to a C terminus comprised of three RING finger domains [69]. MIB1 expression was increased in pancreatic carcinoma tissues and MIB1 overexpression reinforced the proliferative and invasive capacity through the ubiquitin-proteasome pathway [70]. Seo et al. [71] found that MIB1 was responsible for the proteasomal degradation-dependent regulation of α-actinin 3 in skeletal muscle maintenance. Recently, Qin et al. reported that MIB1 overexpression relieved apoptosis and inflammation of cardiac microvascular endothelial cells during coronary microvascular dysfunction by targeting the ASK1/p38 pathway [72]. In agreement with the hypothesis, lncZFAS1 overexpression directly interfered with mir590-3p to inhibit TXNIP the MIB1 E3 ubiquitin ligase/NLRP3 pathway [6]. Finally, we consider that LncZFAS1 can be used as an important regulatory target for neuroinflammatory pathways in PD.

In conclusion, LncZFAS1 is involved in inflammation and pyroptosis in PD through the TXNIP/MIB1 E3 ubiquitin ligase/ NLRP3 axis. This study revealed the potential beneficial role of lncZFAS1 in the progression of PD, which might serve as a new research approach to explore the pathogenesis of PD.

This work was supported by the Natural Science Foundation of China (81972148), Beijing Municipal Science and Technology Commission Capital Clinical Feature Applied Research Project (Z181100001718205), National Key Research and Development Program of China (2018YFC0115400), and Beijing Natural Science Foundation of China (7222101).

All authors whose names appear on the submission agree with the version to be published.

The authors declare no competing interests.

1. Calsolaro V, Edison P. Neuroinflammation in Alzheimer’s disease: current evidence and future directions. Alzheimer’s & Dementia. 2016 Jun 1;12(6):719-32.

2. Theoharides TC, Tsilioni I. Amyotrophic lateral sclerosis, neuroinflammation, and cromolyn. Clinical Therapeutics. 2020 Mar 1;42(3):546-9.

3. Saba J, Couselo FL, Bruno J, Carniglia L, Durand D, Lasaga M, et al. Neuroinflammation in Huntington’s disease: A starring role for astrocyte and microglia. Current Neuropharmacology. 2021 Nov 30.

4. das Neves SP, Sousa JC, Sousa N, Cerqueira JJ, Marques F. Altered astrocytic function in experimental neuroinflammation and multiple sclerosis. Glia. 2021 Jun;69(6):1341-68.

5. Hirsch EC, Standaert DG. Ten unsolved questions about neuroinflammation in Parkinson’s disease. Movement Disorders. 2021 Jan;36(1):16-24.

6. Zhu Z, Huang P, Sun R, Li X, Li W, Gong W. A novel Long-noncoding RNA LncZFAS1 prevents MPP+-induced neuroinflammation through MIB1 activation. Molecular Neurobiology. 2022 Feb;59(2):778-99.

7. Patricio F, Juárez-Torres D, Patricio-Martínez A, Mendieta L, Pérez- Severiano F, Montes S, et al. The C-terminal domain of the heavy chain of tetanus toxin prevents the oxidative and nitrosative stress induced by acute toxicity of 1-methyl-4-phenylpyridinium, a rat model of Parkinson’s disease. Neuroscience Research. 2022 Jan 1;174:36-45.

8. Mangano EN, Peters S, Litteljohn D, So R, Bethune C, Bobyn J, et al. Granulocyte macrophage-colony stimulating factor protects against substantia nigra dopaminergic cell loss in an environmental toxin model of Parkinson’s disease. Neurobiology of Disease. 2011 Jul 1;43(1):99-112.

9. Han J, Kim SJ, Ryu MJ, Jang Y, Lee MJ, Ju X, et al. Chloramphenicol Mitigates Oxidative Stress by Inhibiting Translation of Mitochondrial Complex I in Dopaminergic Neurons of Toxin-Induced Parkinson’s Disease Model. Oxidative Medicine and Cellular Longevity. 2019 Aug 26;2019.

10. Kleinknecht A, Popova B, Lázaro DF, Pinho R, Valerius O, Outeiro TF, et al. C-terminal tyrosine residue modifications modulate the protective phosphorylation of serine 129 of α-synuclein in a yeast model of Parkinson’s disease. PLoS Genetics. 2016 Jun 24;12(6):e1006098.

11. Popova B, Kleinknecht A, Arendarski P, Mischke J, Wang D, Braus GH. Sumoylation protects against β-synuclein toxicity in yeast. Frontiers in Molecular Neuroscience. 2018 Mar 27;11:94.

12. Chia SJ, Tan EK, Chao YX. Historical perspective: Models of Parkinson’s disease. International Journal of Molecular Sciences. 2020 Jan;21(7):2464.

13. Boronat-García A, Guerra-Crespo M, Drucker-Colín R. Historical perspective of cell transplantation in Parkinson’s disease. World Journal of Transplantation. 2017 Jun 24;7(3):179.

14. Tu L, Wu ZY, Yang XL, Zhang Q, Gu R, Wang Q, et al. Neuroprotective effect and mechanism of baicalin on Parkinson’s disease model induced by 6-OHDA. Neuropsychiatric Disease and Treatment. 2019;15:3615.

15. Vijayanathan Y, Lim FT, Lim SM, Long CM, Tan MP, Majeed AB, Ramasamy K. 6-OHDA-lesioned adult zebrafish as a useful Parkinson’s disease model for dopaminergic neuroregeneration. Neurotoxicity Research. 2017 Oct;32(3):496-508.

16. Maegawa H, Niwa H. Generation of mitochondrial toxin rodent models of Parkinson’s disease using 6-OHDA, MPTP, and rotenone. InExperimental Models of Parkinson’s Disease. 2021: 95-110.

17. Hamadjida A, Frouni I, Kwan C, Huot P. Classic animal models of Parkinson’s disease: A historical perspective. Behavioural Pharmacology. 2019 Jun 1;30(4):291-310.

18. Menezes R, Tenreiro S, Macedo D, Santos CN, Outeiro TF. From the baker to the bedside: yeast models of Parkinson’s disease. Microbial Cell. 2015 Aug 3;2(8):262.

19. Zhang L, Zhang L, Li L, Hölscher C. Semaglutide is neuroprotective and reduces α-synuclein levels in the chronic MPTP mouse model of Parkinson’s disease. Journal of Parkinson’s disease. 2019 Jan 1;9(1):157-71.

20. Bazzu G, Calia G, Puggioni G, Spissu Y, Rocchitta G, Debetto P, et al. α-Synuclein-and MPTP-Generated Rodent Models of Parkinson’s Disease and the Study of Extracellular Striatal Dopamine Dynamics: A Microdialysis Approach. CNS & Neurological Disorders-Drug Targets (Formerly Current Drug Targets-CNS & Neurological Disorders). 2010 Aug 1;9(4):482-90.

21. Zhu YL, Sun MF, Jia XB, Cheng K, Xu YD, Zhou ZL, et al. Neuroprotective effects of Astilbin on MPTP-induced Parkinson’s disease mice: Glial reaction, α-synuclein expression and oxidative stress. International Immunopharmacology. 2019 Jan 1;66:19-27.

22. Liu J, Liu W, Li R, Yang H. Mitophagy in Parkinson’s disease: from pathogenesis to treatment. Cells. 2019 Jul;8(7):712.

23. Kovalevich J, Santerre M, Langford D. Considerations for the Use of SH-SY5Y Neuroblastoma Cells in Neurobiology. InNeuronal Cell Culture 2021; 9-23.

24. Zhang T, Gygi SP, Paulo JA. Temporal proteomic profiling of SHSY5Y differentiation with retinoic acid using FAIMS and real-time searching. Journal of Proteome Research. 2020 Oct 15;20(1):704-14.

25. Teppola H, Sarkanen JR, Jalonen TO, Linne ML. Morphological differentiation towards neuronal phenotype of SH-SY5Y neuroblastoma cells by estradiol, retinoic acid and cholesterol. Neurochemical Research. 2016 Apr;41(4):731-47.

26. Paik S, Somvanshi RK, Kumar U. Somatostatin-mediated changes in microtubule-associated proteins and retinoic acid–induced neurite outgrowth in SH-SY5Y cells. Journal of Molecular Neuroscience. 2019 May;68(1):120-34.

27. Xicoy H, Wieringa B, Martens GJ. The SH-SY5Y cell line in Parkinson’s disease research: a systematic review. Molecular Neurodegeneration. 2017 Dec;12(1):1-1.

28. Mosley RL, Hutter-Saunders JA, Stone DK, Gendelman HE. Inflammation and adaptive immunity in Parkinson’s disease. Cold Spring Harbor perspectives in medicine. 2012 Jan 1;2(1):a009381.

29. Askarian-Amiri ME, Crawford J, French JD, Smart CE, Smith MA, Clark MB, et al. SNORD-host RNA Zfas1 is a regulator of mammary development and a potential marker for breast cancer. RNA. 2011 May 1;17(5):878-91.

30. Saijo K, Glass CK. Microglial cell origin and phenotypes in health and disease. Nature Reviews Immunology. 2011 Nov;11(11):775-87.

31. Lee E, Hwang I, Park S, Hong S, Hwang B, Cho Y, et al. MPTP-driven NLRP3 inflammasome activation in microglia plays a central role in dopaminergic neurodegeneration. Cell Death & Differentiation. 2019 Feb;26(2):213-28.

32. Qin Y, Qiu J, Wang P, Liu J, Zhao Y, Jiang F, Lou H. Impaired autophagy in microglia aggravates dopaminergic neurodegeneration by regulating NLRP3 inflammasome activation in experimental models of Parkinson’s disease. Brain, behavior, and immunity. 2021 Jan 1;91:324-38.

33. Wang K, Lu C, Wang T, Qiao C, Lu L, Wu D, et al. Hyperoside suppresses NLRP3 inflammasome in Parkinson’s disease via Pituitary Adenylate Cyclase-Activating Polypeptide. Neurochemistry International. 2022 Jan 1;152:105254.

34. de Araújo FM, Cuenca-Bermejo L, Fernández-Villalba E, Costa SL, Silva VD, Herrero MT. Role of microgliosis and NLRP3 inflammasome in Parkinson’s disease pathogenesis and therapy. Cellular and Molecular Neurobiology. 2021 Jan 2:1-8.

35. Yan YQ, Fang Y, Zheng R, Pu JL, Zhang BR. NLRP3 Inflammasomes in Parkinson’s disease and their Regulation by Parkin. Neuroscience. 2020 Oct 15;446:323-34.

36. Wang S, Yuan YH, Chen NH, Wang HB. The mechanisms of NLRP3 inflammasome/pyroptosis activation and their role in Parkinson’s disease. International Immunopharmacology. 2019 Feb 1;67:458-64.

37. Mao Z, Liu C, Ji S, Yang Q, Ye H, Han H, et al. The NLRP3 inflammasome is involved in the pathogenesis of Parkinson’s disease in rats. Neurochemical Research. 2017 Apr;42(4):1104-15.

38. Panicker N, Kanthasamy A, Kanthasamy AG. Fyn amplifies NLRP3 inflammasome signaling in Parkinson’s disease. Aging (Albany NY). 2019 Aug 31;11(16):5871.

39. Wang S, Yuan YH, Chen NH, Wang HB. The mechanisms of NLRP3 inflammasome/pyroptosis activation and their role in Parkinson’s disease. International Immunopharmacology. 2019 Feb 1;67:458-64.

40. Sarkar S, Malovic E, Harishchandra DS, Ghaisas S, Panicker N, Charli A, et al. Mitochondrial impairment in microglia amplifies NLRP3 inflammasome proinflammatory signaling in cell culture and animal models of Parkinson’s disease. npj Parkinson’s Disease. 2017 Oct 17;3(1):1-5.

41. von Herrmann KM, Salas LA, Martinez EM, Young AL, Howard JM, Feldman MS, et al. NLRP3 expression in mesencephalic neurons and characterization of a rare NLRP3 polymorphism associated with decreased risk of Parkinson’s disease. NPJ Parkinson’s disease. 2018 Aug 15;4(1):1-9.

42. Liu Q, Zhang D, Hu D, Zhou X, Zhou Y. The role of mitochondria in NLRP3 inflammasome activation. Molecular Immunology. 2018 Nov 1;103:115-24.

43. He Y, Hara H, Núñez G. Mechanism and regulation of NLRP3 inflammasome activation. Trends in Biochemical Sciences. 2016 Dec 1;41(12):1012-21.

44. Li Y, Yang G, Yang X, Wang W, Zhang J, He Y, et al. Nicotinic acid inhibits NLRP3 inflammasome activation via SIRT1 in vascular endothelial cells. International Immunopharmacology. 2016 Nov 1;40:211-8.

45. Ge C, Cheng Y, Fan Y, He Y. Vincristine attenuates cardiac fibrosis through the inhibition of NLRP3 inflammasome activation. Clinical Science. 2021 Jun 11;135(11):1409-26.

46. Chen DI, Dixon BJ, Doycheva DM, Li B, Zhang Y, Hu Q, et al. IRE1α inhibition decreased TXNIP/NLRP3 inflammasome activation through miR-17-5p after neonatal hypoxic–ischemic brain injury in rats. Journal of Neuroinflammation. 2018 Dec;15(1):1-8.

47. Tang T, Gong T, Jiang W, Zhou R. GPCRs in NLRP3 inflammasome activation, regulation, and therapeutics. Trends in pharmacological sciences. 2018 Sep 1;39(9):798-811.

48. Swanson KV, Deng M, Ting JP. The NLRP3 inflammasome: molecular activation and regulation to therapeutics. Nature Reviews Immunology. 2019 Aug;19(8):477-89.

49. Di A, Xiong S, Ye Z, Malireddi RS, Kometani S, Zhong M, et al. The TWIK2 potassium efflux channel in macrophages mediates NLRP3 inflammasome-induced inflammation. Immunity. 2018 Jul 17;49(1):56-65.

50. Katsnelson MA, Rucker LG, Russo HM, Dubyak GR. K+ efflux agonists induce NLRP3 inflammasome activation independently of Ca2+ signaling. The Journal of Immunology. 2015 Apr 15;194(8):3937- 52.

51. Katsnelson MA, Lozada-Soto KM, Russo HM, Miller BA, Dubyak GR. NLRP3 inflammasome signaling is activated by low-level lysosome disruption but inhibited by extensive lysosome disruption: roles for K+ efflux and Ca2+ influx. American Journal of Physiology- Cell Physiology. 2016 Jul 1;311(1):C83-100.

52. Zhong Z, Liang S, Sanchez-Lopez E, He F, Shalapour S, Lin XJ, et al. New mitochondrial DNA synthesis enables NLRP3 inflammasome activation. Nature. 2018 Aug;560(7717):198-203.

53. Truax AD, Chen L, Tam JW, Cheng N, Guo H, Koblansky AA, et al. The inhibitory innate immune sensor NLRP12 maintains a threshold against obesity by regulating gut microbiota homeostasis. Cell Host & Microbe. 2018 Sep 12;24(3):364-78.

54. Chen J, Chen ZJ. PtdIns4P on dispersed trans-Golgi network mediates NLRP3 inflammasome activation. Nature. 2018 Dec;564(7734):71-6.

55. Nasoohi S, Ismael S, Ishrat T. Thioredoxin-interacting protein (TXNIP) in cerebrovascular and neurodegenerative diseases: regulation and implication. Molecular Neurobiology. 2018 Oct;55(10):7900-20.

56. Samidurai M, Palanisamy BN, Carot AB, Zenitsky G, Jin H, Anantharam V, et al. PKC delta activation promotes Endoplasmic Reticulum Stress (ERS) and NLR family pyrin domain-containing 3 (NLRP3) inflammasome activation subsequent to αSynuclein-induced microglial activation: Involvement of Thioredoxin-interacting protein (TXNIP)/Thioredoxin (Trx) redoxisome pathway. Frontiers in Aging Neuroscience. 2021;13:377.

57. Ghafouri-Fard S, Kamali MJ, Abak A, Shoorei H, Taheri M. LncRNA ZFAS1: Role in tumorigenesis and other diseases. Biomedicine & Pharmacotherapy. 2021 Oct 1;142:111999.

58. Ye Y, Gao X, Yang N. LncRNA ZFAS1 promotes cell migration and invasion of fibroblast-like synoviocytes by suppression of miR-27a in rheumatoid arthritis. Human Cell. 2018 Jan;31(1):14-21.

59. Jiang Y, Zhang W. LncRNA ZFAS1 plays a role in regulating the inflammatory responses in sepsis-induced acute lung injury via mediating miR-193a-3p. Infection, Genetics and Evolution. 2021 Aug 1;92:104860.

60. An L, Yang T, Zhong Y, Yin Y, Li W, Gao H. Molecular pathways in sepsis-induced cardiomyocyte pyroptosis: Novel finding on long non-coding RNA ZFAS1/miR-138–5p/SESN2 axis. Immunology Letters. 2021 Oct 1;238:47-56.

61. Tang X, Yin R, Shi H, Wang X, Shen D, Wang X, et al. LncRNA ZFAS1 confers inflammatory responses and reduces cholesterol efflux in atherosclerosis through regulating miR-654-3p-ADAM10/RAB22A axis. International Journal of Cardiology. 2020 Sep 15;315:72-80.

62. Feng J, Zhou Z, Feng R, Zeng C, Wei M, Hong T. Silencing long non-coding RNA zinc finger antisense 1 restricts secondary cerebral edema and neuron injuries after traumatic brain injury. Neuroscience Letters. 2021 Jun 21;756:135958.

63. Hu F, Shao L, Zhang J, Zhang H, Wen A, Zhang P. Knockdown of ZFAS1 inhibits hippocampal neurons apoptosis and autophagy by activating the PI3K/AKT pathway via up-regulating miR-421 in epilepsy. Neurochemical Research. 2020 Oct;45(10):2433-41.

64. Wang G, Zhou Y, Zhong T, Song A, Xue Q. The role of blood lnc-ZFAS1 in acute ischemic stroke: correlation with neurological impairment, inflammation, and survival profiles. Journal of clinical Laboratory Analysis. 2022 Feb;36(2):e24219.

65. Zhang Y, Zhang Y. lncRNA ZFAS1 improves neuronal injury and inhibits inflammation, oxidative stress, and apoptosis by sponging miR-582 and upregulating NOS3 expression in cerebral ischemia/ reperfusion injury. Inflammation. 2020 Aug;43(4):1337-50.

66. Braga L, Ali H, Secco I, Giacca M. Non-coding RNA therapeutics for cardiac regeneration. Cardiovascular Research. 2021 Mar 1;117(3):674-93.

67. Vinuesa CG, Rigby RJ, Yu D. Logic and extent of miRNA-mediated control of autoimmune gene expression. International Reviews of Immunology. 2009 Jan 1;28(3-4):112-38.

68. Liu JJ, Li Y, Yang MS, Chen R, Cen CQ. SP1-induced ZFAS1 aggravates sepsis-induced cardiac dysfunction via miR-590–3p/ NLRP3-mediated autophagy and pyroptosis. Archives of Biochemistry and Biophysics. 2020 Nov 30;695:108611.

69. Sarbanes SL, Blomen VA, Lam E, Heissel S, Luna JM, Brummelkamp TR, et al. E3 ubiquitin ligase Mindbomb 1 facilitates nuclear delivery of adenovirus genomes. Proceedings of the National Academy of Sciences. 2021 Jan 5;118(1).

70. Zhang B, Cheng X, Zhan S, Jin X, Liu T. MIB1 upregulates IQGAP1 and promotes pancreatic cancer progression by inducing ST7 degradation. Molecular Oncology. 2021 Nov;15(11):3062-75.

71. Seo JY, Kang JS, Kim YL, Jo YW, Kim JH, Hann SH, et al. Maintenance of type 2 glycolytic myofibers with age by Mib1-Actn3 axis. Nature Communications. 2021 Feb 26;12(1):1-5.

72. Qin XF, Shan YG, Gao JH, Li FX, Guo YX. E3 ubiquitin ligase mind bomb 1 overexpression reduces apoptosis and inflammation of cardiac microvascular endothelial cells in coronary microvascular dysfunction. Cellular Signalling. 2022 Mar 1;91:110223.