{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:32:58Z","timestamp":1790371978499,"version":"4.1.0"},"reference-count":91,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T00:00:00Z","timestamp":1682640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neuroinflammation plays a fundamental role in the development and progression of neurodegenerative diseases. It could therefore be said that neuroinflammation in neurodegenerative pathologies is not a consequence but a cause of them and could represent a therapeutic target of neuronal degeneration. CX3CL1 and several proteases (ADAMs\/MMPs) are strongly involved in the inflammatory pathways of these neurodegenerative pathologies with multiple effects. On the one hand, ADAMs have neuroprotective and anti-apoptotic effects; on the other hand, they target cytokines and chemokines, thus causing inflammatory processes and, consequently, neurodegeneration. CX3CL1 itself is a cytokine substrate for the ADAM, ADAM17, which cleaves and releases it in a soluble isoform (sCX3CL1). CX3CL1, as an adhesion molecule, on the one hand, plays an inhibiting role in the pro-inflammatory response in the central nervous system (CNS) and shows neuroprotective effects by binding its membrane receptor (CX3CR1) present into microglia cells and maintaining them in a quiescent state; on the other hand, the sCX3CL1 isoform seems to promote neurodegeneration. In this review, the dual roles of CX3CL1 and ADAMs\/MMPs in different neurodegenerative diseases, such as Alzheimer\u2019s disease (AD), Parkinson\u2019s disease (PD), Huntington\u2019s disease (MH), and multiple sclerosis (MS), are investigated.<\/jats:p>","DOI":"10.3390\/ijms24098026","type":"journal-article","created":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T10:51:52Z","timestamp":1682679112000},"page":"8026","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["The Cytokine CX3CL1 and ADAMs\/MMPs in Concerted Cross-Talk Influencing Neurodegenerative Diseases"],"prefix":"10.3390","volume":"24","author":[{"given":"Matilda","family":"Iemmolo","sequence":"first","affiliation":[{"name":"Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, 90128 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7250-9808","authenticated-orcid":false,"given":"Giulio","family":"Ghersi","sequence":"additional","affiliation":[{"name":"Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, 90128 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1723-3305","authenticated-orcid":false,"given":"Giulia","family":"Bivona","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neurosciences and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, University of Palermo, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1124\/mi.10.5.3","article-title":"Fractalkine\/CX3CL1: A Potential New Target for Inflammatory Diseases","volume":"10","author":"Jones","year":"2010","journal-title":"Mol. Interv."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2944","DOI":"10.1111\/febs.14466","article-title":"A guide to chemokines and their receptors","volume":"285","author":"Hughes","year":"2018","journal-title":"FEBS J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1056\/NEJM199802123380706","article-title":"Chemokines\u2014Chemotactic Cytokines That Mediate Inflammation","volume":"338","author":"Luster","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e147","DOI":"10.1002\/mco2.147","article-title":"Role of chemokine systems in cancer and inflammatory diseases","volume":"3","author":"Li","year":"2022","journal-title":"Medcomm"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"15213","DOI":"10.18632\/oncotarget.14773","article-title":"CX3CL1: A potential chemokine widely involved in the process spinal metastases","volume":"8","author":"Liu","year":"2017","journal-title":"Oncotarget"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"10896","DOI":"10.1073\/pnas.95.18.10896","article-title":"Role for neuronally derived fractalkine in mediating interactions between neurons and CX3CR1-expressing microglia","volume":"95","author":"Harrison","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Pawelec, P., Ziemka-Nalecz, M., Sypecka, J., and Zalewska, T. (2020). The Impact of the CX3CL1\/CX3CR1 Axis in Neurological Disorders. Cells, 9.","DOI":"10.3390\/cells9102277"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1161\/01.ATV.0000095360.62479.1F","article-title":"Fractalkine in Vascular Biology: From basic research to clinical disease","volume":"24","author":"Umehara","year":"2004","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1182\/blood-2002-12-3775","article-title":"The disintegrin-like metalloproteinase ADAM10 is involved in constitutive cleavage of CX3CL1 (fractalkine) and regulates CX3CL1-mediated cell-cell adhesion","volume":"102","author":"Hundhausen","year":"2003","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1186\/s12974-016-0659-7","article-title":"Fractalkine shedding is mediated by p38 and the ADAM10 protease under pro-inflammatory conditions in human astrocytes","volume":"13","author":"Gasparini","year":"2016","journal-title":"J. Neuroinflamm."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4833","DOI":"10.1523\/JNEUROSCI.5221-09.2010","article-title":"The Disintegrin\/Metalloproteinase ADAM10 Is Essential for the Establishment of the Brain Cortex","volume":"30","author":"Jorissen","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e12748","DOI":"10.7554\/eLife.12748","article-title":"Systematic substrate identification indicates a central role for the metalloprotease ADAM10 in axon targeting and synapse function","volume":"5","author":"Kuhn","year":"2016","journal-title":"Elife"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Costa, S., Ragusa, M.A., Buglio, G.L., Scilabra, S.D., and Nicosia, A. (2022). The Repertoire of Tissue Inhibitors of Metalloproteases: Evolution, Regulation of Extracellular Matrix Proteolysis, Engineering and Therapeutic Challenges. Life, 12.","DOI":"10.3390\/life12081145"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1016\/j.cell.2017.11.014","article-title":"Structural Basis for Regulated Proteolysis by the \u03b1-Secretase ADAM10","volume":"171","author":"Seegar","year":"2017","journal-title":"Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1084\/jem.20182238","article-title":"The intracellular domain of CX3CL1 regulates adult neurogenesis and Alzheimer\u2019s amyloid pathology","volume":"216","author":"Fan","year":"2019","journal-title":"J. Exp. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"37993","DOI":"10.1074\/jbc.M106434200","article-title":"Tumor Necrosis Factor-\u03b1-converting Enzyme (ADAM17) Mediates the Cleavage and Shedding of Fractalkine (CX3CL1)*","volume":"276","author":"Garton","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1016\/S0735-1097(00)00827-5","article-title":"Expression of tumor necrosis factor-alpha\u2013converting enzyme and tumor necrosis factor-alpha in human myocarditis","volume":"36","author":"Satoh","year":"2000","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4570","DOI":"10.4049\/jimmunol.160.9.4570","article-title":"TNF-\u03b1 Convertase Enzyme from Human Arthritis-Affected Cartilage: Isolation of cDNA by Differential Display, Expression of the Active Enzyme, and Regulation of TNF-\u03b1","volume":"160","author":"Patel","year":"1998","journal-title":"J. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.bbrc.2007.04.100","article-title":"Sequential processing of the transmembrane chemokines CX3CL1 and CXCL16 by \u03b1- and \u03b3-secretases","volume":"358","author":"Schulte","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1038\/19083","article-title":"A presenilin-1-dependent \u03b3-secretase-like protease mediates release of Notch intracellular domain","volume":"398","author":"Annaert","year":"1999","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"70","DOI":"10.3389\/fncel.2015.00070","article-title":"Regulation of cerebral cortical neurogenesis by the Pax6 transcription factor","volume":"9","author":"Manuel","year":"2015","journal-title":"Front. Cell. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3231","DOI":"10.1242\/dev.01893","article-title":"SMAD pathway mediation of BDNF and TGF\u03b22 regulation of proliferation and differentiation of hippocampal granule neurons","volume":"132","author":"Lu","year":"2005","journal-title":"Development"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1016\/j.febslet.2012.03.023","article-title":"TGF-\u03b2 control of stem cell differentiation genes","volume":"586","author":"Xi","year":"2012","journal-title":"FEBS Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1186\/s12974-020-01828-y","article-title":"Two forms of CX3CL1 display differential activity and rescue cognitive deficits in CX3CL1 knockout mice","volume":"17","author":"Winter","year":"2020","journal-title":"J. Neuroinflamm."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1038\/s41593-019-0419-y","article-title":"Sensory lesioning induces microglial synapse elimination via ADAM10 and fractalkine signaling","volume":"22","author":"Gunner","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.jneuroim.2008.04.012","article-title":"Neuron-microglia signaling: Chemokines as versatile messengers","volume":"198","author":"Biber","year":"2008","journal-title":"J. Neuroimmunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.neuron.2012.03.026","article-title":"Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner","volume":"74","author":"Schafer","year":"2012","journal-title":"Neuron"},{"key":"ref_28","first-page":"1628","article-title":"Related Content Characterization of Fractalkine in Rat Brain Cells: Migratory and Activation Signals for CX 3 CR-1-Expressing Microglia Combinatorial Model of Chemokine Involvement in Glomerular Monocyte Recruitment: Role of CXC Chemokine Receptor 2 in Innltration During Nephrotoxic Nephritis","volume":"163","author":"Chen","year":"1999","journal-title":"J. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e5","DOI":"10.4110\/in.2018.18.e5","article-title":"Tissue-specific Role of CX3CR1 Expressing Immune Cells and Their Relationships with Human Disease","volume":"18","author":"Lee","year":"2018","journal-title":"Immune Netw."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1126\/science.1110647","article-title":"Neuroscience: Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo","volume":"308","author":"Nimmerjahn","year":"2005","journal-title":"Science"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1038\/nn1715","article-title":"Control of microglial neurotoxicity by the fractalkine receptor","volume":"9","author":"Cardona","year":"2006","journal-title":"Nat. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1007\/s10571-015-0232-4","article-title":"The Distinct Role of ADAM17 in APP Proteolysis and Microglial Activation Related to Alzheimer\u2019s Disease","volume":"36","author":"Qian","year":"2015","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3055","DOI":"10.1007\/s00018-019-03173-7","article-title":"Functions of \u2019A disintegrin and metalloproteases (ADAMs)\u2019 in the mammalian nervous system","volume":"76","author":"Hsia","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"107989","DOI":"10.1016\/j.pharmthera.2021.107989","article-title":"CX3CL1\/CX3CR1 signaling targets for the treatment of neurodegenerative diseases","volume":"231","author":"Subbarayan","year":"2021","journal-title":"Pharmacol. Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"14592","DOI":"10.1523\/JNEUROSCI.0539-12.2012","article-title":"The Soluble Isoform of CX3CL1 Is Necessary for Neuroprotection in a Mouse Model of Parkinson\u2019s Disease","volume":"32","author":"Morganti","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/mt.2014.175","article-title":"Fractalkine Over Expression Suppresses \u03b1-Synuclein-mediated Neurodegeneration","volume":"23","author":"Nash","year":"2015","journal-title":"Mol. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.3233\/JAD-161123","article-title":"Dynamics of the Complement, Cytokine, and Chemokine Systems in the Regulation of Synaptic Function and Dysfunction Relevant to Alzheimer\u2019s Disease","volume":"57","author":"Jiang","year":"2017","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.neuron.2010.08.023","article-title":"Regulation of Tau Pathology by the Microglial Fractalkine Receptor","volume":"68","author":"Bhaskar","year":"2010","journal-title":"Neuron"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s13024-017-0200-1","article-title":"Absence of CX3CR1 impairs the internalization of Tau by microglia","volume":"12","author":"Perea","year":"2017","journal-title":"Mol. Neurodegener."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"549","DOI":"10.3389\/fneur.2018.00549","article-title":"Roles of Microglial and Monocyte Chemokines and Their Receptors in Regulating Alzheimer\u2019s Disease-Associated Amyloid-\u03b2 and Tau Pathologies","volume":"9","author":"Guedes","year":"2018","journal-title":"Front. Neurol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.neuropharm.2009.11.010","article-title":"Targeting p38 MAPK pathway for the treatment of Alzheimer\u2019s disease","volume":"58","author":"Munoz","year":"2010","journal-title":"Neuropharmacology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1515\/revneuro-2018-0008","article-title":"Role of p38\/MAPKs in Alzheimer\u2019s disease: Implications for amyloid beta toxicity targeted therapy","volume":"30","author":"Kheiri","year":"2019","journal-title":"Rev. Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1590\/s0102-865020180070000007","article-title":"NF-kB mediated CX3CL1 activation in the dorsal root ganglion contributes to the maintenance of neuropathic pain induced in adult male Sprague Dawley rats","volume":"33","author":"Liu","year":"2018","journal-title":"Acta Cir. Bras."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3","DOI":"10.2174\/1871527316666170807130011","article-title":"NF-\u03baB as a Key Mediator of Brain Inflammation in Alzheimer\u2019s Disease","volume":"18","author":"Hwang","year":"2017","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.jns.2016.05.022","article-title":"Upstream regulators and downstream effectors of NF-\u03baB in Alzheimer\u2019s disease","volume":"366","author":"Shi","year":"2016","journal-title":"J. Neurol. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"709","DOI":"10.2174\/1567205017666201109095657","article-title":"Cerebrospinal Fluid and Blood CX3CL1 as a Potential Biomarker in Early Diagnosis and Prognosis of Dementia","volume":"17","author":"Mroczko","year":"2020","journal-title":"Curr. Alzheimer Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1016\/j.neurobiolaging.2012.12.011","article-title":"Fractalkine overexpression suppresses tau pathology in a mouse model of tauopathy","volume":"34","author":"Nash","year":"2013","journal-title":"Neurobiol. Aging"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"202","DOI":"10.2174\/156720508783954749","article-title":"Regulation of \u03b2APP and PrPc Cleavage by \u03b1-Secretase: Mechanistic and Therapeutic Perspectives","volume":"5","author":"Vincent","year":"2008","journal-title":"Curr. Alzheimer Res."},{"key":"ref_49","first-page":"146","article-title":"ADAM-17: The enzyme that does it all. Crit. Rev. Biochem","volume":"45","author":"Gooz","year":"2010","journal-title":"Mol. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1038\/s41380-018-0091-8","article-title":"A rare loss-of-function variant of ADAM17 is associated with late-onset familial Alzheimer disease","volume":"25","author":"Hartl","year":"2018","journal-title":"Mol. Psychiatry"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3987","DOI":"10.1093\/hmg\/ddp323","article-title":"Potential late-onset Alzheimer\u2019s disease-associated mutations in the ADAM10 gene attenuate \u03b1-secretase activity","volume":"18","author":"Kim","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1172\/JCI20864","article-title":"A disintegrin-metalloproteinase prevents amyloid plaque formation and hippocampal defects in an Alzheimer disease mouse model","volume":"113","author":"Postina","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"27765","DOI":"10.1074\/jbc.273.43.27765","article-title":"Evidence That Tumor Necrosis Factor \u03b1 Converting Enzyme Is Involved in Regulated \u03b1-Secretase Cleavage of the Alzheimer Amyloid Protein Precursor","volume":"273","author":"Buxbaum","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1056\/NEJMoa1211851","article-title":"TREM2 Variants in Alzheimer\u2019s Disease","volume":"368","author":"Guerreiro","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"117345","DOI":"10.1016\/j.lfs.2020.117345","article-title":"The benefits and mechanisms of exercise training for Parkinson\u2019s disease","volume":"245","author":"Feng","year":"2020","journal-title":"Life Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1016\/S0140-6736(21)00218-X","article-title":"Parkinson\u2019s disease","volume":"397","author":"Bloem","year":"2021","journal-title":"Lancet"},{"key":"ref_57","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_58","first-page":"102340","article-title":"Massage therapy as a complementary treatment for Parkinson\u2019s disease: A Systematic Literature Review. Complement","volume":"49","author":"Angelopoulou","year":"2020","journal-title":"Ther. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/1742-2094-8-9","article-title":"CX3CL1 reduces neurotoxicity and microglial activation in a rat model of Parkinson\u2019s disease","volume":"8","author":"Pabon","year":"2011","journal-title":"J. Neuroinflamm."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1007\/s12640-015-9557-5","article-title":"CX3CR1 Disruption Differentially Influences Dopaminergic Neuron Degeneration in Parkinsonian Mice Depending on the Neurotoxin and Route of Administration","volume":"29","author":"Lazzarini","year":"2016","journal-title":"Neurotox. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/s12974-022-02481-3","article-title":"Parkinson\u2019s disease peripheral immune biomarker profile: A multicentre, cross-sectional and longitudinal study","volume":"19","author":"Li","year":"2022","journal-title":"J. Neuroinflamm."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/s11011-021-00801-9","article-title":"Serum fractalkine and 3-nitrotyrosine levels correlate with disease severity in Parkinson\u2019s disease: A pilot study","volume":"37","author":"Gupta","year":"2022","journal-title":"Metab. Brain Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e3319","DOI":"10.1002\/jgm.3319","article-title":"Association of ADAM10 gene variants with sporadic Parkinson\u2019s disease in Chinese Han population","volume":"23","author":"Zhou","year":"2021","journal-title":"J. Gene Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1007\/s12640-019-00031-z","article-title":"Genetic Association Between NGFR, ADAM17 Gene Polymorphism, and Parkinson\u2019s Disease in the Chinese Han Population","volume":"36","author":"Li","year":"2019","journal-title":"Neurotox. Res."},{"key":"ref_65","first-page":"973298","article-title":"Association of aBACE1Gene Polymorphism with Parkinson\u2019s Disease in a Norwegian Population","volume":"2015","author":"Lange","year":"2015","journal-title":"Park. Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/nrneurol.2014.37","article-title":"Mechanisms of neurodegeneration and axonal dysfunction in multiple sclerosis","volume":"10","author":"Friese","year":"2014","journal-title":"Nat. Rev. Neurol."},{"key":"ref_67","first-page":"a028936","article-title":"Multiple Sclerosis Pathology. Cold Spring Harb","volume":"8","author":"Lassmann","year":"2018","journal-title":"Perspect. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/ene.13819","article-title":"Multiple sclerosis\u2014A review","volume":"26","author":"Dobson","year":"2019","journal-title":"Eur. J. Neurol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1093\/jnen\/62.9.899","article-title":"CX3CL1 and CX3CR1 Expression in Human Brain Tissue: Noninflammatory Control versus Multiple Sclerosis","volume":"62","author":"Hulshof","year":"2003","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1742-2094-2-17","article-title":"CX3CL1 (fractalkine) and CX3CR1 expression in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis: Kinetics and cellular origin","volume":"2","author":"Sunnemark","year":"2005","journal-title":"J. Neuroinflamm."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.clim.2015.01.001","article-title":"The role of fractalkine (CX3CL1) in regulation of CD4+ cell migration to the central nervous system in patients with relapsing\u2013remitting multiple sclerosis","volume":"157","author":"Blauth","year":"2015","journal-title":"Clin. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.jaut.2011.11.006","article-title":"CX3CR1 drives cytotoxic CD4+CD28\u2212 T cells into the brain of multiple sclerosis patients","volume":"38","author":"Broux","year":"2012","journal-title":"J. Autoimmun."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1186\/1742-2094-9-193","article-title":"Extracellular adenosine signaling induces CX3CL1 expression in the brain to promote experimental autoimmune encephalomyelitis","volume":"9","author":"Mills","year":"2012","journal-title":"J. Neuroinflamm."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"5409","DOI":"10.1073\/pnas.1316510111","article-title":"Pharmacological inhibition of the chemokine receptor CX3CR1 attenuates disease in a chronic-relapsing rat model for multiple sclerosis","volume":"111","author":"Ekerot","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1084\/jem.20141656","article-title":"Inefficient clearance of myelin debris by microglia impairs remyelinating processes","volume":"212","author":"Lampron","year":"2015","journal-title":"J. Exp. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1155\/2013\/480702","article-title":"Elevated Expression of Fractalkine (CX3CL1) and Fractalkine Receptor (CX3CR1) in the Dorsal Root Ganglia and Spinal Cord in Experimental Autoimmune Encephalomyelitis: Implications in Multiple Sclerosis-Induced Neuropathic Pain","volume":"2013","author":"Zhu","year":"2013","journal-title":"BioMed. Res. Int."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1191\/135248506ms1276oa","article-title":"Upregulation of ADAM-17 expression in active lesions in multiple sclerosis","volume":"12","author":"Plumb","year":"2006","journal-title":"Mult. Scler. J."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1002\/glia.10226","article-title":"ADAM-10 and ADAM-17 in the inflamed human CNS","volume":"42","author":"Kieseier","year":"2003","journal-title":"Glia"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3097","DOI":"10.1007\/s00018-019-03174-6","article-title":"MMPs and ADAMs in neurological infectious diseases and multiple sclerosis","volume":"76","author":"Muri","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1038\/35081571","article-title":"Metalloproteinases in biology and pathology of the nervous system","volume":"2","author":"Yong","year":"2001","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1093\/brain\/124.9.1743","article-title":"The expression profile of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in lesions and normal appearing white matter of multiple sclerosis","volume":"124","author":"Lindberg","year":"2001","journal-title":"Brain"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1093\/arclin\/acx086","article-title":"The Neuropsychology of Huntington\u2019s Disease","volume":"32","author":"Snowden","year":"2017","journal-title":"Arch. Clin. Neuropsychol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1111\/ene.13413","article-title":"Huntington\u2019s disease: A clinical review","volume":"25","author":"McColgan","year":"2018","journal-title":"Eur. J. Neurol."},{"key":"ref_84","first-page":"1030","article-title":"Molecular Pathogenesis in Huntington\u2019s Disease","volume":"83","author":"Illarioshkin","year":"2018","journal-title":"Biochemistry"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.csbj.2016.02.001","article-title":"Network analysis of human post-mortem microarrays reveals novel genes, microRNAs, and mechanistic scenarios of potential importance in fighting huntington\u2019s disease","volume":"14","author":"Chandrasekaran","year":"2016","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"193","DOI":"10.3389\/fnagi.2017.00193","article-title":"Microglial Activation in the Pathogenesis of Huntington\u2019s Disease","volume":"9","author":"Yang","year":"2017","journal-title":"Front. Aging Neurosci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"163","DOI":"10.3389\/fncel.2020.00163","article-title":"Reduced Fractalkine Levels Lead to Striatal Synaptic Plasticity Deficits in Huntington\u2019s Disease","volume":"14","author":"Kim","year":"2020","journal-title":"Front. Cell. Neurosci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"736","DOI":"10.3389\/fnins.2017.00736","article-title":"Altered Expression of Matrix Metalloproteinases and Their Endogenous Inhibitors in a Human Isogenic Stem Cell Model of Huntington\u2019s Disease","volume":"11","author":"Naphade","year":"2018","journal-title":"Front. Neurosci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.neuron.2010.06.021","article-title":"Matrix Metalloproteinases Are Modifiers of Huntingtin Proteolysis and Toxicity in Huntington\u2019s Disease","volume":"67","author":"Miller","year":"2010","journal-title":"Neuron"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1111\/j.1365-2990.2010.01157.x","article-title":"Role of matrix metalloproteinase-9 (MMP-9) in striatal blood-brain barrier disruption in a 3-nitropropionic acid model of Huntington\u2019s disease","volume":"37","author":"Manich","year":"2011","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.neuroscience.2016.03.031","article-title":"Enhanced immune response to MMP3 stimulation in microglia expressing mutant huntingtin","volume":"325","author":"Connolly","year":"2016","journal-title":"Neuroscience"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/9\/8026\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:25:51Z","timestamp":1760124351000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/9\/8026"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,28]]},"references-count":91,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["ijms24098026"],"URL":"https:\/\/doi.org\/10.3390\/ijms24098026","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,28]]}}}