{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:18:46Z","timestamp":1791901126062,"version":"4.3.4"},"reference-count":84,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T00:00:00Z","timestamp":1717718400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"German Academic Exchange Service to Hilal Cihankaya"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron degeneration in the central nervous system. Recent research has increasingly linked the activation of nucleotide oligomerization domain-like receptor protein 3 (NLRP3) inflammasome to ALS pathogenesis. NLRP3 activation triggers Caspase 1 (CASP 1) auto-activation, leading to the cleavage of Gasdermin D (GSDMD) and pore formation on the cellular membrane. This process facilitates cytokine secretion and ultimately results in pyroptotic cell death, highlighting the complex interplay of inflammation and neurodegeneration in ALS. This study aimed to characterize the NLRP3 inflammasome components and their colocalization with cellular markers using the wobbler mouse as an ALS animal model. Firstly, we checked the levels of miR-223-3p because of its association with NLRP3 inflammasome activity. The wobbler mice showed an increased expression of miR-223-3p in the ventral horn, spinal cord, and cerebellum tissues. Next, increased levels of NLRP3, pro-CASP 1, cleaved CASP 1 (c-CASP 1), full-length GSDMD, and cleaved GDSMD revealed NLRP3 inflammasome activation in wobbler spinal cords, but not in the cerebellum. Furthermore, we investigated the colocalization of the aforementioned proteins with neurons, microglia, and astrocyte markers in the spinal cord tissue. Evidently, the wobbler mice displayed microgliosis, astrogliosis, and motor neuron degeneration in this tissue. Additionally, we showed the upregulation of protein levels and the colocalization of NLRP3, c-CASP1, and GSDMD in neurons, as well as in microglia and astrocytes. Overall, this study demonstrated the involvement of NLRP3 inflammasome activation and pyroptotic cell death in the spinal cord tissue of wobbler mice, which could further exacerbate the motor neuron degeneration and neuroinflammation in this ALS mouse model.<\/jats:p>","DOI":"10.3390\/cells13120995","type":"journal-article","created":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T10:43:42Z","timestamp":1717757022000},"page":"995","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Elevated NLRP3 Inflammasome Activation Is Associated with Motor Neuron Degeneration in ALS"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3475-0585","authenticated-orcid":false,"given":"Hilal","family":"Cihankaya","sequence":"first","affiliation":[{"name":"Department of Cytology, Institute of Anatomy, Ruhr-University Bochum, 44801 Bochum, Germany"},{"name":"International Graduate School of Neuroscience (IGSN), Ruhr-University Bochum, 44801 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verian","family":"Bader","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology, Institute of Biochemistry and Pathobiochemistry, Medical Faculty, Ruhr-University Bochum, 44801 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstanze F.","family":"Winklhofer","sequence":"additional","affiliation":[{"name":"International Graduate School of Neuroscience (IGSN), Ruhr-University Bochum, 44801 Bochum, Germany"},{"name":"Department of Molecular Cell Biology, Institute of Biochemistry and Pathobiochemistry, Medical Faculty, Ruhr-University Bochum, 44801 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1782-4642","authenticated-orcid":false,"given":"Matthias","family":"Vorgerd","sequence":"additional","affiliation":[{"name":"Department of Neurology, Heimer Institute for Muscle Research, University Hospital Bergmannsheil, Ruhr-University Bochum, Buerkle-de-la-Camp-Platz 1, 44789 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4878-8741","authenticated-orcid":false,"given":"Johann","family":"Matschke","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology (Cancer Research), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Stahlke","sequence":"additional","affiliation":[{"name":"Department of Cytology, Institute of Anatomy, Ruhr-University Bochum, 44801 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7983-0143","authenticated-orcid":false,"given":"Carsten","family":"Theiss","sequence":"additional","affiliation":[{"name":"Department of Cytology, Institute of Anatomy, Ruhr-University Bochum, 44801 Bochum, Germany"},{"name":"International Graduate School of Neuroscience (IGSN), Ruhr-University Bochum, 44801 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9717-4485","authenticated-orcid":false,"given":"Veronika","family":"Matschke","sequence":"additional","affiliation":[{"name":"Department of Cytology, Institute of Anatomy, Ruhr-University Bochum, 44801 Bochum, Germany"},{"name":"International Graduate School of Neuroscience (IGSN), Ruhr-University Bochum, 44801 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"E613","DOI":"10.1212\/WNL.0000000000207474","article-title":"Global Prevalence and Incidence of Amyotrophic Lateral Sclerosis: A Systematic Review","volume":"101","author":"Wolfson","year":"2023","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1038\/nrneurol.2011.152","article-title":"Molecular Pathways of Motor Neuron Injury in Amyotrophic Lateral Sclerosis","volume":"7","author":"Ferraiuolo","year":"2011","journal-title":"Nat. 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