{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:11:19Z","timestamp":1785431479440,"version":"3.56.0"},"reference-count":101,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"crossref","award":["25-74-10090"],"award-info":[{"award-number":["25-74-10090"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"crossref"}]},{"award":["25-74-10090"],"award-info":[{"award-number":["25-74-10090"]}],"id":[{"id":"https:\/\/ror.org\/03y2gwe85","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["NeuroSci"],"abstract":"<jats:p>Background: Cell and mouse models studies demonstrate NLRP3 inflammasome involvement in amyotrophic lateral sclerosis (ALS) neuroinflammation. Peripheral blood mononuclear cells (PBMCs) are a promising, yet understudied, source of in vivo inflammasome activation biomarkers. Our study reviewed the literature on PBMC-based inflammasome studies of ALS and other neurodegenerative diseases and tested different conditions for PBMC handling to evaluate inflammasome and inflammation-related protein expression in these cells. Methods: Expression of NLRP3 inflammasome components and inflammation-related proteins was analyzed by Real-time qPCR and Western blot in non-cultivated\/cultivated PBMCs of 23 ALS patients and 20 Healthy controls. IL-1\u03b2 and IL-18 levels were measured in plasma and cultivated PBMC supernatants by ELISA. Results: Cultivation of PBMCs decreased expression of inflammasome components and inflammation-related cytokines on the mRNA but not protein level. NLRP3 mRNA expression was significantly higher in ALS-cultivated PBMCs. In both ALS and Healthy controls, IL-18 was detected in plasma, and IL-1\u03b2 in supernatants of cultivated PBMCs. Conclusions: Our findings suggest that PBMC handling conditions, i.e., cell cultivation, may determine particular parameters associated with NLRP3 inflammasome expression and activation pathway, so they should be carefully selected for PBMC-based studies of inflammasome in neurodegenerative and non-neurological disorders and taken into account when interpreting the study results.<\/jats:p>","DOI":"10.3390\/neurosci7040084","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T17:13:17Z","timestamp":1784826797000},"page":"84","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["NLRP3 Inflammasome and Inflammation-Related Proteins Expression Characterized in Non-Cultivated Versus Cultivated Peripheral Blood Cells of Patients with Amyotrophic Lateral Sclerosis"],"prefix":"10.3390","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1334-9730","authenticated-orcid":false,"given":"Denis","family":"Shevchuk","sequence":"first","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Str., 32, 119991 Moscow, Russia"},{"name":"Russian Center of Neurology and Neurosciences, Volokolamskoye Shosse, 80, 125367 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulia","family":"Kuzmenko","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Str., 32, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariya","family":"Zakharova","sequence":"additional","affiliation":[{"name":"Russian Center of Neurology and Neurosciences, Volokolamskoye Shosse, 80, 125367 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vadim","family":"Karpov","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Str., 32, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2183-0858","authenticated-orcid":false,"given":"Elizaveta","family":"Starodubova","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Str., 32, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2260-6551","authenticated-orcid":false,"given":"Anastasia","family":"Latanova","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Str., 32, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17071","DOI":"10.1038\/nrdp.2017.71","article-title":"Amyotrophic Lateral Sclerosis","volume":"3","author":"Hardiman","year":"2017","journal-title":"Nat. Rev. Dis. Primer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4693","DOI":"10.1007\/s00415-024-12435-9","article-title":"Update on Recent Advances in Amyotrophic Lateral Sclerosis","volume":"271","author":"Riva","year":"2024","journal-title":"J. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1080\/21678421.2016.1188961","article-title":"Riluzole Exerts Transient Modulating Effects on Cortical and Axonal Hyperexcitability in ALS","volume":"17","author":"Geevasinga","year":"2016","journal-title":"Amyotroph. Lateral Scler. Front. Degener."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1136\/jnnp-2015-312908","article-title":"A Clinical Tool for Predicting Survival in ALS","volume":"87","author":"Knibb","year":"2016","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"P\u00e9ladeau, C., and Sandhu, J.K. (2021). Aberrant NLRP3 Inflammasome Activation Ignites the Fire of Inflammation in Neuromuscular Diseases. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22116068"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Liu, E., Karpf, L., and Bohl, D. (2021). Neuroinflammation in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia and the Interest of Induced Pluripotent Stem Cells to Study Immune Cells Interactions With Neurons. Front. Mol. Neurosci., 14.","DOI":"10.3389\/fnmol.2021.767041"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1097\/WCO.0000000000001279","article-title":"Neuroinflammation in Amyotrophic Lateral Sclerosis: Pathogenic Insights and Therapeutic Implications","volume":"37","author":"Calma","year":"2024","journal-title":"Curr. Opin. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5864391","DOI":"10.1155\/2023\/5864391","article-title":"PET and SPECT Imaging of ALS: An Educational Review","volume":"2023","author":"Jamali","year":"2023","journal-title":"Mol. Imaging"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2288","DOI":"10.1016\/j.cell.2023.04.025","article-title":"A 360\u00b0 View of the Inflammasome: Mechanisms of Activation, Cell Death, and Diseases","volume":"186","author":"Barnett","year":"2023","journal-title":"Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1038\/s41423-021-00670-3","article-title":"An Update on the Regulatory Mechanisms of NLRP3 Inflammasome Activation","volume":"18","author":"Paik","year":"2021","journal-title":"Cell. Mol. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Dai, Z., Liu, W.-C., Chen, X.-Y., Wang, X., Li, J.-L., and Zhang, X. (2023). Gasdermin D-Mediated Pyroptosis: Mechanisms, Diseases, and Inhibitors. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1178662"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Moreno-Garc\u00eda, L., Miana-Mena, F.J., Moreno-Mart\u00ednez, L., de la Torre, M., Lunetta, C., Tarlarini, C., Zaragoza, P., Calvo, A.C., and Osta, R. (2021). Inflammasome in ALS Skeletal Muscle: NLRP3 as a Potential Biomarker. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052523"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2260","DOI":"10.1002\/glia.22891","article-title":"NLRP3 Inflammasome Is Expressed by Astrocytes in the SOD1 Mouse Model of ALS and in Human Sporadic ALS Patients","volume":"63","author":"Johann","year":"2015","journal-title":"Glia"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1002\/glia.23728","article-title":"The Microglial NLRP3 Inflammasome Is Activated by Amyotrophic Lateral Sclerosis Proteins","volume":"68","author":"Deora","year":"2020","journal-title":"Glia"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1111\/bpa.12467","article-title":"Neurodegeneration and NLRP3 Inflammasome Expression in the Anterior Thalamus of SOD1(G93A) ALS Mice","volume":"28","author":"Debye","year":"2018","journal-title":"Brain Pathol. Zur. Switz."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.neuroscience.2021.03.023","article-title":"Expression and Cell Type-Specific Localization of Inflammasome Sensors in the Spinal Cord of SOD1(G93A) Mice and Sporadic Amyotrophic Lateral Sclerosis Patients","volume":"463","author":"Hummel","year":"2021","journal-title":"Neuroscience"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1126\/science.288.5464.335","article-title":"Functional Role of Caspase-1 and Caspase-3 in an ALS Transgenic Mouse Model","volume":"288","author":"Li","year":"2000","journal-title":"Science"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"13046","DOI":"10.1073\/pnas.1002396107","article-title":"Mutant Superoxide Dismutase 1-Induced IL-1beta Accelerates ALS Pathogenesis","volume":"107","author":"Meissner","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4004","DOI":"10.1007\/s12035-023-03315-w","article-title":"Inflammasome-Mediated Neuronal-Microglial Crosstalk: A Therapeutic Substrate for the Familial C9orf72 Variant of Frontotemporal Dementia\/Amyotrophic Lateral Sclerosis","volume":"60","author":"Trageser","year":"2023","journal-title":"Mol. Neurobiol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Cl\u00e9net, M.-L., Keaney, J., Gillet, G., Valadas, J.S., Langlois, J., Cardenas, A., Gasser, J., and Kadiu, I. (2023). Divergent Functional Outcomes of NLRP3 Blockade Downstream of Multi-Inflammasome Activation: Therapeutic Implications for ALS. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1190219"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2542998","DOI":"10.1080\/17590914.2025.2542998","article-title":"Dysregulated Expression of Inflammasome and Extracellular Matrix Genes in C9orf72-ALS\/FTD Microglia","volume":"17","author":"Thiry","year":"2025","journal-title":"ASN Neuro"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"eabq0651","DOI":"10.1126\/sciadv.abq0651","article-title":"Cell-Autonomous Immune Dysfunction Driven by Disrupted Autophagy in C9orf72-ALS iPSC-Derived Microglia Contributes to Neurodegeneration","volume":"9","author":"Banerjee","year":"2023","journal-title":"Sci. Adv."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s12974-022-02421-1","article-title":"ALS Monocyte-Derived Microglia-like Cells Reveal Cytoplasmic TDP-43 Accumulation, DNA Damage, and Cell-Specific Impairment of Phagocytosis Associated with Disease Progression","volume":"19","author":"Quek","year":"2022","journal-title":"J. Neuroinflammation"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Fu, R.-H., Tsai, C.-W., Chiu, S.-C., Liu, S.-P., Chiang, Y.-T., Kuo, Y.-H., Shyu, W.-C., and Lin, S.-Z. (2022). C9-ALS-Associated Proline-Arginine Dipeptide Repeat Protein Induces Activation of NLRP3 Inflammasome of HMC3 Microglia Cells by Binding of Complement Component 1 Q Subcomponent-Binding Protein (C1QBP), and Syringin Prevents This Effect. Cells, 11.","DOI":"10.3390\/cells11193128"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/s00401-022-02466-9","article-title":"Increased Pyroptosis Activation in White Matter Microglia Is Associated with Neuronal Loss in ALS Motor Cortex","volume":"144","author":"Ospitalieri","year":"2022","journal-title":"Acta Neuropathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/1742-2094-11-94","article-title":"Evaluating the Levels of Interleukin-1 Family Cytokines in Sporadic Amyotrophic Lateral Sclerosis","volume":"11","author":"Italiani","year":"2014","journal-title":"J. Neuroinflamm."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"19796","DOI":"10.1038\/s41598-024-67165-9","article-title":"Inflammatory Signature in Amyotrophic Lateral Sclerosis Predicting Disease Progression","volume":"14","author":"Femiano","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5941","DOI":"10.1038\/s41598-020-62756-8","article-title":"Peripheral Proinflammatory Th1\/Th17 Immune Cell Shift Is Linked to Disease Severity in Amyotrophic Lateral Sclerosis","volume":"10","author":"Jin","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1089\/brain.2020.0741","article-title":"Amyotrophic Lateral Sclerosis Blood Cytokines Are Altered, but Do Not Correlate with Changes in Brain Topology","volume":"10","author":"Polverino","year":"2020","journal-title":"Brain Connect."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1002\/acn3.51078","article-title":"Longitudinal Biomarkers in Amyotrophic Lateral Sclerosis","volume":"7","author":"Huang","year":"2020","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Tzeplaeff, L., J\u00fcrs, A.V., Wohnrade, C., and Demleitner, A.F. (2024). Unraveling the Heterogeneity of ALS-A Call to Redefine Patient Stratification for Better Outcomes in Clinical Trials. Cells, 13.","DOI":"10.3390\/cells13050452"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1002\/mus.26801","article-title":"Addressing Heterogeneity in Amyotrophic Lateral Sclerosis CLINICAL TRIALS","volume":"62","author":"Goyal","year":"2020","journal-title":"Muscle Nerve"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1002\/glia.20467","article-title":"Systemic LPS Causes Chronic Neuroinflammation and Progressive Neurodegeneration","volume":"55","author":"Qin","year":"2007","journal-title":"Glia"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.brainresrev.2007.02.003","article-title":"Molecular Networks of Brain and Immunity","volume":"55","author":"Goncharova","year":"2007","journal-title":"Brain Res. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Sun, Y., Koyama, Y., and Shimada, S. (2022). Inflammation From Peripheral Organs to the Brain: How Does Systemic Inflammation Cause Neuroinflammation? Front. Aging Neurosci., 14.","DOI":"10.3389\/fnagi.2022.903455"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"156974","DOI":"10.1016\/j.cyto.2025.156974","article-title":"A Comprehensive Review: Neuroinflammation and Immune Communication between the Central Nervous System and the Periphery","volume":"192","author":"Kaur","year":"2025","journal-title":"Cytokine"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"17423","DOI":"10.1038\/s41598-024-67177-5","article-title":"Alzheimer\u2019s Disease Metabolomics Consortium Peripheral Inflammation Is Associated with Brain Atrophy and Cognitive Decline Linked to Mild Cognitive Impairment and Alzheimer\u2019s Disease","volume":"14","author":"Liang","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Beltran-Velasco, A.I., and Clemente-Su\u00e1rez, V.J. (2025). Impact of Peripheral Inflammation on Blood-Brain Barrier Dysfunction and Its Role in Neurodegenerative Diseases. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26062440"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1007\/s00401-010-0786-7","article-title":"Cytoplasmic Accumulation of TDP-43 in Circulating Lymphomonocytes of ALS Patients with and without TARDBP Mutations","volume":"121","author":"Lupino","year":"2011","journal-title":"Acta Neuropathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1111\/nan.12328","article-title":"Monocytes of Patients with Amyotrophic Lateral Sclerosis Linked to Gene Mutations Display Altered TDP-43 Subcellular Distribution","volume":"43","author":"Lomartire","year":"2017","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Browne, D.J., Miller, C.M., and Doolan, D.L. (2024). Technical Pitfalls When Collecting, Cryopreserving, Thawing, and Stimulating Human T-Cells. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1382192"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Kiefer, J., Zeller, J., Bogner, B., H\u00f6rbrand, I.A., Lang, F., Deiss, E., Winninger, O., Fricke, M., Kreuzaler, S., and Smudde, E. (2021). An Unbiased Flow Cytometry-Based Approach to Assess Subset-Specific Circulating Monocyte Activation and Cytokine Profile in Whole Blood. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.641224"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1111\/j.1699-0463.1997.tb05048.x","article-title":"Characteristics of CD14 Shedding from Human Monocytes. Evidence for the Competition of Soluble CD14 (sCD14) with CD14 Receptors for Lipopolysaccharide (LPS) Binding","volume":"105","author":"Rokita","year":"1997","journal-title":"APMIS Acta Pathol. Microbiol. Immunol. Scand."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"La Rosa, F., Zoia, C.P., Bazzini, C., Bolognini, A., Saresella, M., Conti, E., Ferrarese, C., Piancone, F., Marventano, I., and Galimberti, D. (2022). Modulation of MAPK- and PI3\/AKT-Dependent Autophagy Signaling by Stavudine (D4T) in PBMC of Alzheimer\u2019s Disease Patients. Cells, 11.","DOI":"10.3390\/cells11142180"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.bbi.2008.07.003","article-title":"Peripheral Cytokines Profile in Parkinson\u2019s Disease","volume":"23","author":"Reale","year":"2009","journal-title":"Brain. Behav. Immun."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Codolo, G., Plotegher, N., Pozzobon, T., Brucale, M., Tessari, I., Bubacco, L., and de Bernard, M. (2013). Triggering of Inflammasome by Aggregated \u03b1-Synuclein, an Inflammatory Response in Synucleinopathies. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0055375"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"White, A.J., Wijeyekoon, R.S., Scott, K.M., Gunawardana, N.P., Hayat, S., Solim, I.H., McMahon, H.T., Barker, R.A., and Williams-Gray, C.H. (2018). The Peripheral Inflammatory Response to Alpha-Synuclein and Endotoxin in Parkinson\u2019s Disease. Front. Neurol., 9.","DOI":"10.3389\/fneur.2018.00946"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Piancone, F., Saresella, M., La Rosa, F., Marventano, I., Meloni, M., Navarro, J., and Clerici, M. (2021). Inflammatory Responses to Monomeric and Aggregated \u03b1-Synuclein in Peripheral Blood of Parkinson Disease Patients. Front. Neurosci., 15.","DOI":"10.3389\/fnins.2021.639646"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5916","DOI":"10.1007\/s00415-024-12554-3","article-title":"Immune Responses to Oligomeric \u03b1-Synuclein in Parkinson\u2019s Disease Peripheral Blood Mononuclear Cells","volume":"271","author":"Porcedda","year":"2024","journal-title":"J. Neurol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1186\/s12974-021-02329-2","article-title":"Systemic Inflammasome Activation and Pyroptosis Associate with the Progression of Amnestic Mild Cognitive Impairment and Alzheimer\u2019s Disease","volume":"18","author":"Rui","year":"2021","journal-title":"J. Neuroinflamm."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/S0753-3322(99)80079-1","article-title":"IL-1 Beta, IL-2, IL-6 and TNF-Alpha Production by Peripheral Blood Mononuclear Cells from Patients with Parkinson\u2019s Disease","volume":"53","author":"Bessler","year":"1999","journal-title":"Biomed. Pharmacother. Biomed. Pharmacother."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1034\/j.1600-0404.2000.101003159.x","article-title":"Impaired Cytokine Production by Peripheral Blood Mononuclear Cells and Monocytes\/Macrophages in Parkinson\u2019s Disease","volume":"101","author":"Hasegawa","year":"2000","journal-title":"Acta Neurol. Scand."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s12974-019-1670-6","article-title":"Systemic Activation of NLRP3 Inflammasome and Plasma \u03b1-Synuclein Levels Are Correlated with Motor Severity and Progression in Parkinson\u2019s Disease","volume":"17","author":"Fan","year":"2020","journal-title":"J. Neuroinflamm."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2648","DOI":"10.1111\/ene.14918","article-title":"P2X7 Receptor\/NLRP3 Inflammasome Complex and \u03b1-Synuclein in Peripheral Blood Mononuclear Cells: A Prospective Study in Neo-Diagnosed, Treatment-Na\u00efve Parkinson\u2019s Disease","volume":"28","author":"Solini","year":"2021","journal-title":"Eur. J. Neurol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1001\/jamaneurol.2017.0357","article-title":"Characterization of Gene Expression Phenotype in Amyotrophic Lateral Sclerosis Monocytes","volume":"74","author":"Zhao","year":"2017","journal-title":"JAMA Neurol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1975","DOI":"10.1016\/j.clinph.2020.04.005","article-title":"A Proposal for New Diagnostic Criteria for ALS","volume":"131","author":"Shefner","year":"2020","journal-title":"Clin. Neurophysiol. Off. J. Int. Fed. Clin. Neurophysiol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Li, Z., and Gong, C. (2025). NLRP3 Inflammasome in Alzheimer\u2019s Disease: Molecular Mechanisms and Emerging Therapies. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1583886"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"7296","DOI":"10.1007\/s12035-025-04715-w","article-title":"Research Progress in the Molecular Mechanism of NLRP3 Inflammasome in Alzheimer\u2019s Disease and Regulation by Natural Plant Products","volume":"62","author":"Zu","year":"2025","journal-title":"Mol. Neurobiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"115167","DOI":"10.1016\/j.expneurol.2025.115167","article-title":"Targeting the NLRP3 Inflammasome in Parkinson\u2019s Disease: From Molecular Mechanism to Therapeutic Strategy","volume":"386","author":"Liang","year":"2025","journal-title":"Exp. Neurol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2657","DOI":"10.1007\/s10787-025-01733-x","article-title":"Exploring the Therapeutic Potential of NLRP3 Inhibitors in Parkinson\u2019s Disease: A Systematic Review of in-Vivo Studies","volume":"33","author":"Sadier","year":"2025","journal-title":"Inflammopharmacology"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Nagar, A., Bharadwaj, R., Shaikh, M.O.F., and Roy, A. (2023). What Are NLRP3-ASC Specks? An Experimental Progress of 22 Years of Inflammasome Research. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1188864"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s13024-016-0088-1","article-title":"The NLRP3 and NLRP1 Inflammasomes Are Activated in Alzheimer\u2019s Disease","volume":"11","author":"Saresella","year":"2016","journal-title":"Mol. Neurodegener."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4210","DOI":"10.4049\/jimmunol.1700352","article-title":"Cutting Edge: Distinct Regulatory Mechanisms Control Proinflammatory Cytokines IL-18 and IL-1\u03b2","volume":"198","author":"Zhu","year":"2017","journal-title":"J. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"167253","DOI":"10.1016\/j.jmb.2021.167253","article-title":"Transcriptional and Epigenetic Regulation of Gasdermins","volume":"434","author":"Bourdonnay","year":"2022","journal-title":"J. Mol. Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"39920","DOI":"10.1074\/jbc.M007255200","article-title":"Expression Analysis of the Human Caspase-1 Subfamily Reveals Specific Regulation of the CASP5 Gene by Lipopolysaccharide and Interferon-Gamma","volume":"275","author":"Lin","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1007\/s00018-016-2396-6","article-title":"Assembly and Regulation of ASC Specks","volume":"74","author":"Hoss","year":"2017","journal-title":"Cell. Mol. Life Sci. CMLS"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Novick, D. (2024). IL-18 and IL-18BP: A Unique Dyad in Health and Disease. Int. J. Mol. Sci., 25.","DOI":"10.20944\/preprints202411.0864.v1"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/S1074-7613(00)80013-8","article-title":"Interleukin-18 Binding Protein: A Novel Modulator of the Th1 Cytokine Response","volume":"10","author":"Novick","year":"1999","journal-title":"Immunity"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2282","DOI":"10.4049\/jimmunol.168.5.2282","article-title":"IL-12 Induces Monocyte IL-18 Binding Protein Expression via IFN-Gamma","volume":"168","author":"Veenstra","year":"2002","journal-title":"J. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1093\/cvr\/cvq076","article-title":"The Nuclear Factor-kappaB-Interleukin-6 Signalling Pathway Mediating Vascular Inflammation","volume":"86","author":"Brasier","year":"2010","journal-title":"Cardiovasc. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"8815","DOI":"10.1073\/pnas.0402800101","article-title":"Differences in Signaling Pathways by IL-1beta and IL-18","volume":"101","author":"Lee","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1007\/s11064-023-04085-6","article-title":"The Role of IL-6 in Neurodegenerative Disorders","volume":"49","author":"Shan","year":"2024","journal-title":"Neurochem. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"787","DOI":"10.4049\/jimmunol.0901363","article-title":"Cutting Edge: NF-kappaB Activating Pattern Recognition and Cytokine Receptors License NLRP3 Inflammasome Activation by Regulating NLRP3 Expression","volume":"183","author":"Bauernfeind","year":"2009","journal-title":"J. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Gritsenko, A., Yu, S., Martin-Sanchez, F., Diaz-Del-Olmo, I., Nichols, E.-M., Davis, D.M., Brough, D., and Lopez-Castejon, G. (2020). Priming Is Dispensable for NLRP3 Inflammasome Activation in Human Monocytes In Vitro. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.565924"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1111\/nan.12483","article-title":"Expression Profile of Pattern Recognition Receptors in Skeletal Muscle of SOD1(G93A) Amyotrophic Lateral Sclerosis (ALS) Mice and Sporadic ALS Patients","volume":"44","author":"Lehmann","year":"2018","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"140581","DOI":"10.1016\/j.bbapap.2020.140581","article-title":"The Impact of Blood-Processing Time on the Proteome of Human Peripheral Blood Mononuclear Cells","volume":"1869","author":"Bonilauri","year":"2021","journal-title":"Biochim. Biophys. Acta Proteins Proteom."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.jim.2007.02.003","article-title":"Defining Blood Processing Parameters for Optimal Detection of Cryopreserved Antigen-Specific Responses for HIV Vaccine Trials","volume":"322","author":"Bull","year":"2007","journal-title":"J. Immunol. Methods"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"BSR20203827","DOI":"10.1042\/BSR20203827","article-title":"Effects of Storage Time and Temperature on Highly Multiparametric Flow Analysis of Peripheral Blood Samples; Implications for Clinical Trial Samples","volume":"41","author":"Jerram","year":"2021","journal-title":"Biosci. Rep."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1016\/j.tcb.2021.05.004","article-title":"Stress Relief: Emerging Methods to Mitigate Dissociation-Induced Artefacts","volume":"31","author":"Machado","year":"2021","journal-title":"Trends Cell Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1089\/bio.2010.0009","article-title":"Gene Expression Profiles from Peripheral Blood Mononuclear Cells Are Sensitive to Short Processing Delays","volume":"8","author":"Barnes","year":"2010","journal-title":"Biopreserv. Biobank."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/s13059-020-02032-0","article-title":"Sampling Time-Dependent Artifacts in Single-Cell Genomics Studies","volume":"21","author":"Iacono","year":"2020","journal-title":"Genome Biol."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Gautam, A., Donohue, D., Hoke, A., Miller, S.A., Srinivasan, S., Sowe, B., Detwiler, L., Lynch, J., Levangie, M., and Hammamieh, R. (2019). Investigating Gene Expression Profiles of Whole Blood and Peripheral Blood Mononuclear Cells Using Multiple Collection and Processing Methods. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0225137"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Liu, Z., Ouyang, T., Yang, Y., Sheng, Y., Shi, H., Liu, Q., Bai, Y., and Ge, Q. (2024). The Impact of Blood Sample Processing on Ribonucleic Acid (RNA) Sequencing. Genes, 15.","DOI":"10.3390\/genes15040502"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1189\/jlb.0313153","article-title":"Cellular Stress Response and Innate Immune Signaling: Integrating Pathways in Host Defense and Inflammation","volume":"94","author":"Muralidharan","year":"2013","journal-title":"J. Leukoc. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1038\/nprot.2006.268","article-title":"Intracellular Cytokine Optimization and Standard Operating Procedure","volume":"1","author":"Lamoreaux","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"113514","DOI":"10.1016\/j.jim.2023.113514","article-title":"Impact of Delayed PBMC Processing on Functional and Genomic Assays","volume":"519","author":"Yi","year":"2023","journal-title":"J. Immunol. Methods"},{"key":"ref_87","first-page":"99","article-title":"Fetal Bovine Serum (FBS): Past\u2014Present\u2014Future","volume":"35","author":"Bieback","year":"2018","journal-title":"Altex"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1126\/science.abm1317","article-title":"Fetal Bovine Serum-a Cell Culture Dilemma","volume":"375","year":"2022","journal-title":"Science"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/nrg3185","article-title":"Insights into the Regulation of Protein Abundance from Proteomic and Transcriptomic Analyses","volume":"13","author":"Vogel","year":"2012","journal-title":"Nat. Rev. Genet."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/gb-2003-4-9-117","article-title":"Comparing Protein Abundance and mRNA Expression Levels on a Genomic Scale","volume":"4","author":"Greenbaum","year":"2003","journal-title":"Genome Biol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1007\/s00401-014-1345-4","article-title":"Inflammatory Dysregulation of Blood Monocytes in Parkinson\u2019s Disease Patients","volume":"128","author":"Grozdanov","year":"2014","journal-title":"Acta Neuropathol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1038\/nature04515","article-title":"Cryopyrin Activates the Inflammasome in Response to Toxins and ATP","volume":"440","author":"Mariathasan","year":"2006","journal-title":"Nature"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"135279","DOI":"10.1016\/j.neulet.2020.135279","article-title":"Beta-Amyloid Activates NLRP3 Inflammasome via TLR4 in Mouse Microglia","volume":"736","author":"Liu","year":"2020","journal-title":"Neurosci. Lett."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.cyto.2018.07.026","article-title":"Soluble A\u03b21-42 Suppresses TNF-\u03b1 and Activates NLRP3 Inflammasome in THP-1 Macrophages","volume":"111","author":"Gupta","year":"2018","journal-title":"Cytokine"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"115735","DOI":"10.1016\/j.biopha.2023.115735","article-title":"The Interplay between \u03b1-Synuclein and NLRP3 Inflammasome in Parkinson\u2019s Disease","volume":"168","author":"Huang","year":"2023","journal-title":"Biomed. Pharmacother. Biomed. Pharmacother."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1182\/blood.V91.2.577","article-title":"Lipopolysaccharide Activates Caspase-1 (Interleukin-1-Converting Enzyme) in Cultured Monocytic and Endothelial Cells","volume":"91","author":"Schumann","year":"1998","journal-title":"Blood"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"e28553","DOI":"10.1016\/j.heliyon.2024.e28553","article-title":"Serum Cytokines Profile Changes in Amyotrophic Lateral Sclerosis","volume":"10","author":"Xu","year":"2024","journal-title":"Heliyon"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"9094","DOI":"10.1038\/s41598-017-09097-1","article-title":"Increased Peripheral Blood Inflammatory Cytokine Levels in Amyotrophic Lateral Sclerosis: A Meta-Analysis Study","volume":"7","author":"Hu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"37069","DOI":"10.1074\/jbc.M103574200","article-title":"A Novel Role for Interleukin-18 in Adhesion Molecule Induction through NF Kappa B and Phosphatidylinositol (PI) 3-Kinase-Dependent Signal Transduction Pathways","volume":"276","author":"Morel","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1111\/j.1755-5949.2009.00116.x","article-title":"A Review of the Neural Mechanisms of Action and Clinical Efficiency of Riluzole in Treating Amyotrophic Lateral Sclerosis: What Have We Learned in the Last Decade?","volume":"17","author":"Bellingham","year":"2011","journal-title":"CNS Neurosci. Ther."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"134829","DOI":"10.1016\/j.neulet.2020.134829","article-title":"Riluzole Improves Functional Recovery after Acute Spinal Cord Injury in Rats and May Be Associated with Changes in Spinal Microglia\/Macrophages Polarization","volume":"723","author":"Wu","year":"2020","journal-title":"Neurosci. Lett."}],"container-title":["NeuroSci"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2673-4087\/7\/4\/84\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T04:12:32Z","timestamp":1785125552000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2673-4087\/7\/4\/84"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,23]]},"references-count":101,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["neurosci7040084"],"URL":"https:\/\/doi.org\/10.3390\/neurosci7040084","relation":{},"ISSN":["2673-4087"],"issn-type":[{"value":"2673-4087","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,23]]}}}