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While its dysregulation has long been investigated in cancer, fibrosis, and autoimmunity, increasing evidence implicates ECM remodeling in neurodegenerative diseases, including motor neuron diseases (MNDs). Amyotrophic lateral sclerosis and spinal muscular atrophy, the most studied MNDs, both exhibit profound ECM alterations that influence synaptic connectivity, glial reactivity, and neuroinflammation. This review outlines recent data on ECM dynamics in MNDs, highlighting shared and disease-specific mechanisms, their potential as biomarkers, and therapeutic opportunities targeting the ECM environment to preserve neuronal function and slow disease progression.<\/jats:p>","DOI":"10.3390\/ijms262311376","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T08:50:20Z","timestamp":1764060620000},"page":"11376","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Extracellular Matrix Remodeling in Motor Neuron Diseases"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5782-1665","authenticated-orcid":false,"given":"Savina","family":"Apolloni","sequence":"first","affiliation":[{"name":"Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Tortoriello","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy"},{"name":"Institute of Translational Pharmacology (IFT), National Research Council (CNR), 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Milani","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5038-0767","authenticated-orcid":false,"given":"Simona","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy"},{"name":"Institute of Translational Pharmacology (IFT), National Research Council (CNR), 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2830","DOI":"10.1111\/febs.14818","article-title":"The Extracellular Matrix as a Multitasking Player in Disease","volume":"286","author":"Theocharis","year":"2019","journal-title":"FEBS J."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Dzobo, K., and Dandara, C. (2023). The Extracellular Matrix: Its Composition, Function, Remodeling, and Role in Tumorigenesis. Biomimetics, 8.","DOI":"10.20944\/preprints202301.0555.v1"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1038\/nrm3902","article-title":"Extracellular Matrix Assembly: A Multiscale Deconstruction","volume":"15","author":"Mouw","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Nonnast, E., Mira, E., and Ma\u00f1es, S. (2024). Biomechanical Properties of Laminins and Their Impact on Cancer Progression. Biochim. Biophys. Acta (BBA)\u2014Rev. Cancer, 1879.","DOI":"10.1016\/j.bbcan.2024.189181"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S20","DOI":"10.1097\/IJG.0000000000000108","article-title":"Biology of the Extracellular Matrix: An Overview","volume":"23","author":"Yue","year":"2014","journal-title":"J. Glaucoma"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Dalton, C.J., and Lemmon, C.A. (2021). Fibronectin: Molecular Structure, Fibrillar Structure and Mechanochemical Signaling. Cells, 10.","DOI":"10.20944\/preprints202108.0010.v1"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Tr\u0119bacz, H., and Barzycka, A. (2023). Mechanical Properties and Functions of Elastin: An Overview. Biomolecules, 13.","DOI":"10.3390\/biom13030574"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3904","DOI":"10.1111\/j.1742-4658.2010.07800.x","article-title":"Proteoglycans in Health and Disease: Novel Roles for Proteoglycans in Malignancy and Their Pharmacological Targeting","volume":"277","author":"Theocharis","year":"2010","journal-title":"FEBS J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.matbio.2015.02.003","article-title":"Proteoglycan Form and Function: A Comprehensive Nomenclature of Proteoglycans","volume":"42","author":"Iozzo","year":"2015","journal-title":"Matrix Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"C298","DOI":"10.1152\/ajpcell.00913.2024","article-title":"The Stiffness of Extracellular Matrix in Regulating Cellular Metabolism","volume":"329","author":"Zha","year":"2025","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e70281","DOI":"10.1002\/mco2.70281","article-title":"Extracellular Matrix Signaling Cues: Biological Functions, Diseases, and Therapeutic Targets","volume":"6","author":"Zhao","year":"2025","journal-title":"MedComm"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Melrose, J., Hayes, A.J., and Bix, G. (2021). The CNS\/PNS Extracellular Matrix Provides Instructive Guidance Cues to Neural Cells and Neuroregulatory Proteins in Neural Development and Repair. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115583"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1007\/s10571-020-00986-0","article-title":"Extracellular Matrix in Neural Plasticity and Regeneration","volume":"42","author":"Chelyshev","year":"2020","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1111\/j.1460-9568.2011.07690.x","article-title":"Chondroitin Sulfate Proteoglycans Regulate Astrocyte-Dependent Synaptogenesis and Modulate Synaptic Activity in Primary Embryonic Hippocampal Neurons","volume":"33","author":"Pyka","year":"2011","journal-title":"Eur. J. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/978-3-7091-0932-8_7","article-title":"The Brain\u2019s Extracellular Matrix and Its Role in Synaptic Plasticity","volume":"970","author":"Frischknecht","year":"2012","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Auer, S., Schicht, M., Hoffmann, L., Budday, S., Frischknecht, R., Bl\u00fcmcke, I., and Paulsen, F. (2025). The Role of Perineuronal Nets in Physiology and Disease: Insights from Recent Studies. Cells, 14.","DOI":"10.20944\/preprints202501.2221.v1"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ortega, J.A., Soares de Aguiar, G.P., Chandravanshi, P., Levy, N., Engel, E., and \u00c1lvarez, Z. (2024). Exploring the Properties and Potential of the Neural Extracellular Matrix for Next-Generation Regenerative Therapies. WIREs Nanomed. Nanobiotechnol., 16.","DOI":"10.1002\/wnan.1962"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ferrer-Ferrer, M., and Dityatev, A. (2018). Shaping Synapses by the Neural Extracellular Matrix. Front. Neuroanat., 12.","DOI":"10.3389\/fnana.2018.00040"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"H\u00f6hn, L., Hu\u00dfler, W., Richter, A., Smalla, K.-H., Birkl-Toeglhofer, A.-M., Birkl, C., Vielhaber, S., Leber, S.L., Gundelfinger, E.D., and Haybaeck, J. (2023). Extracellular Matrix Changes in Subcellular Brain Fractions and Cerebrospinal Fluid of Alzheimer\u2019s Disease Patients. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065532"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2400480","DOI":"10.1002\/advs.202400480","article-title":"Extracellular Matrix Remodeling Alleviates Memory Deficits in Alzheimer\u2019s Disease by Enhancing the Astrocytic Autophagy-Lysosome Pathway","volume":"11","author":"Yang","year":"2024","journal-title":"Adv. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s00401-012-1042-0","article-title":"Neurochemical Mapping of the Human Hippocampus Reveals Perisynaptic Matrix around Functional Synapses in Alzheimer\u2019s Disease","volume":"125","author":"Lendvai","year":"2013","journal-title":"Acta Neuropathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/s41531-024-00653-x","article-title":"Synaptic Dysfunction and Extracellular Matrix Dysregulation in Dopaminergic Neurons from Sporadic and E326K-GBA1 Parkinson\u2019s Disease Patients","volume":"10","author":"Rosh","year":"2024","journal-title":"npj Park. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Freitas, A., Aroso, M., Barros, A., Fern\u00e1ndez, M., Conde-Sousa, E., Leite, M., Carvalho, E.D., Ribeiro, C.C., Ferreira, R., and P\u00eago, A.P. (2021). Characterization of the Striatal Extracellular Matrix in a Mouse Model of Parkinson\u2019s Disease. Antioxidants, 10.","DOI":"10.3390\/antiox10071095"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1958","DOI":"10.1093\/brain\/awab059","article-title":"The Extracellular Matrix as Modifier of Neuroinflammation and Remyelination in Multiple Sclerosis","volume":"144","author":"Ghorbani","year":"2021","journal-title":"Brain"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Stephenson, E.L., Jain, R.W., Ghorbani, S., Gorter, R.P., D\u2019Mello, C., and Yong, V.W. (2024). Uncovering Novel Extracellular Matrix Transcriptome Alterations in Lesions of Multiple Sclerosis. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25021240"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1002\/jnr.24127","article-title":"Aberrant Astrocytic Expression of Chondroitin Sulfate Proteoglycan Receptors in a Rat Model of Amyotrophic Lateral Sclerosis","volume":"96","author":"Shijo","year":"2018","journal-title":"J. Neurosci. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"104776","DOI":"10.1016\/j.jprot.2022.104776","article-title":"Proteomics Analysis Indicates the Involvement of Immunity and Inflammation in the Onset Stage of SOD1-G93A Mouse Model of ALS","volume":"272","author":"Chen","year":"2023","journal-title":"J. Proteom."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Rossi, S., Milani, M., Della Valle, I., and Apolloni, S. (2025). Transcriptomic Profiling of Symptomatic and End-Stage SOD1-G93A Transgenic Mice Reveals Extracellular Matrix Components as Key Players in ALS Pathogenesis. Biochim. Biophys. Acta (BBA)\u2014Mol. Basis Dis., 1871.","DOI":"10.1016\/j.bbadis.2025.167707"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Cheung, S.W., Willis, E.F., Simmons, D.G., Bellingham, M.C., and Noakes, P.G. (2024). Phagocytosis of Aggrecan-Positive Perineuronal Nets Surrounding Motor Neurons by Reactive Microglia Expressing MMP-9 in TDP-43Q331K ALS Model Mice. Neurobiol. Dis., 200.","DOI":"10.1016\/j.nbd.2024.106614"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Cheung, S.W., Bhavnani, E., Simmons, D.G., Bellingham, M.C., and Noakes, P.G. (2024). Perineuronal Nets Are Phagocytosed by MMP-9 Expressing Microglia and Astrocytes in the SOD1G93A ALS Mouse Model. Neuropathol. Appl. Neurobiol., 50.","DOI":"10.1111\/nan.12982"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Forostyak, S., Forostyak, O., Kwok, J.C.F., Romanyuk, N., Rehorova, M., Kriska, J., Dayanithi, G., Raha-Chowdhury, R., Jendelova, P., and Anderova, M. (2020). Transplantation of Neural Precursors Derived from Induced Pluripotent Cells Preserve Perineuronal Nets and Stimulate Neural Plasticity in ALS Rats. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21249593"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s40035-018-0135-7","article-title":"GM604 Regulates Developmental Neurogenesis Pathways and the Expression of Genes Associated with Amyotrophic Lateral Sclerosis","volume":"7","author":"Swindell","year":"2018","journal-title":"Transl. Neurodegener."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Adachi, K., Miyata, K., Chida, Y., Hirose, M., Morisaki, Y., Yamanaka, K., and Misawa, H. (2023). Depletion of Perivascular Macrophages Delays ALS Disease Progression by Ameliorating Blood-Spinal Cord Barrier Impairment in SOD1G93A Mice. Front. Cell Neurosci., 17.","DOI":"10.3389\/fncel.2023.1291673"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2799","DOI":"10.1093\/hmg\/ddz104","article-title":"Motor Neurons from ALS Patients with Mutations in C9ORF72 and SOD1 Exhibit Distinct Transcriptional Landscapes","volume":"28","author":"Wong","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Lin, J., Huang, P., Chen, W., Ye, C., Su, H., and Yao, X. (2020). Key Molecules and Pathways Underlying Sporadic Amyotrophic Lateral Sclerosis: Integrated Analysis on Gene Expression Profiles of Motor Neurons. Front. Genet., 11.","DOI":"10.3389\/fgene.2020.578143"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Swindell, W.R. (2024). Meta-Analysis of Differential Gene Expression in Lower Motor Neurons Isolated by Laser Capture Microdissection from Post-Mortem ALS Spinal Cords. Front. Genet., 15.","DOI":"10.3389\/fgene.2024.1385114"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1101\/gr.275939.121","article-title":"Meta-Analysis of Human and Mouse ALS Astrocytes Reveals Multi-Omic Signatures of Inflammatory Reactive States","volume":"32","author":"Ziff","year":"2022","journal-title":"Genome Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4893","DOI":"10.1038\/s41467-024-49196-y","article-title":"Multiomic ALS Signatures Highlight Subclusters and Sex Differences Suggesting the MAPK Pathway as Therapeutic Target","volume":"15","author":"Hausmann","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1186\/s13287-024-03820-2","article-title":"Proteomic Analysis of Cerebrospinal Fluid of Amyotrophic Lateral Sclerosis Patients in the Presence of Autologous Bone Marrow Derived Mesenchymal Stem Cells","volume":"15","author":"Reis","year":"2024","journal-title":"Stem Cell Res. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1038\/s41593-024-01589-4","article-title":"PolyGR and polyPR Knock-in Mice Reveal a Conserved Neuroprotective Extracellular Matrix Signature in C9orf72 ALS\/FTD Neurons","volume":"27","author":"Milioto","year":"2024","journal-title":"Nat. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1038\/s41591-021-01295-9","article-title":"Altered Perivascular Fibroblast Activity Precedes ALS Disease Onset","volume":"27","author":"Skene","year":"2021","journal-title":"Nat. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1080\/21678421.2021.1918721","article-title":"Low Plasma Hyaluronan Is Associated with Faster Functional Decline in Patients with Amyotrophic Lateral Sclerosis","volume":"23","author":"Holdom","year":"2022","journal-title":"Amyotroph. Lateral Scler. Front. Degener."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Hu\u00dfler, W., H\u00f6hn, L., Stolz, C., Vielhaber, S., Garz, C., Schmitt, F.C., Gundelfinger, E.D., Schreiber, S., and Seidenbecher, C.I. (2022). Brevican and Neurocan Cleavage Products in the Cerebrospinal Fluid\u2014Differential Occurrence in ALS, Epilepsy and Small Vessel Disease. Front. Cell Neurosci., 16.","DOI":"10.3389\/fncel.2022.838432"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"117175","DOI":"10.1016\/j.jns.2020.117175","article-title":"Matrix Metalloproteinases Deregulation in Amyotrophic Lateral Sclerosis","volume":"419","author":"Espinosa","year":"2020","journal-title":"J. Neurol. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Lu, C., Huang, X., Huang, M., Liu, C., and Xu, J. (2025). Mendelian Randomization of Plasma Proteomics Identifies Novel ALS-Associated Proteins and Their GO Enrichment and KEGG Pathway Analyses. BMC Neurol., 25.","DOI":"10.1186\/s12883-025-04091-x"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1093\/hmg\/ddp506","article-title":"Pre-Symptomatic Development of Lower Motor Neuron Connectivity in a Mouse Model of Severe Spinal Muscular Atrophy","volume":"19","author":"Murray","year":"2010","journal-title":"Human. Mol. Genet."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Kumar, S.H., Brandt, K., Claus, P., and Jung, K. (2024). Comparative Meta-Analysis of Transcriptomic Studies in Spinal Muscular Atrophy: Comparison between Tissues and Mouse Models. BMC Med. Genom., 17.","DOI":"10.1186\/s12920-024-02040-0"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1016\/j.celrep.2019.09.033","article-title":"Interaction of Axonal Chondrolectin with Collagen XIXa1 Is Necessary for Precise Neuromuscular Junction Formation","volume":"29","author":"Smith","year":"2019","journal-title":"Cell Rep."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"B\u00e4umer, D., Lee, S., Nicholson, G., Davies, J.L., Parkinson, N.J., Murray, L.M., Gillingwater, T.H., Ansorge, O., Davies, K.E., and Talbot, K. (2009). Alternative Splicing Events Are a Late Feature of Pathology in a Mouse Model of Spinal Muscular Atrophy. PLoS Genet., 5.","DOI":"10.1371\/journal.pgen.1000773"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.cell.2008.03.031","article-title":"SMN Deficiency Causes Tissue-Specific Perturbations in the Repertoire of snRNAs and Widespread Defects in Splicing","volume":"133","author":"Zhang","year":"2008","journal-title":"Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1093\/hmg\/ddt477","article-title":"Chondrolectin Affects Cell Survival and Neuronal Outgrowth in in Vitro and in Vivo Models of Spinal Muscular Atrophy","volume":"23","author":"Sleigh","year":"2014","journal-title":"Human. Mol. Genet."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e30955","DOI":"10.7554\/eLife.30955","article-title":"Hypoexcitability Precedes Denervation in the Large Fast-Contracting Motor Units in Two Unrelated Mouse Models of ALS","volume":"7","author":"Sharma","year":"2018","journal-title":"eLife"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.nbd.2009.09.006","article-title":"Reduced VGLUT2 Expression Increases Motor Neuron Viability in Sod1G93A Mice","volume":"37","author":"Wootz","year":"2010","journal-title":"Neurobiol. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"278","DOI":"10.14336\/AD.2018.0917","article-title":"Collagen XIX Alpha 1 Improves Prognosis in Amyotrophic Lateral Sclerosis","volume":"10","author":"Calvo","year":"2019","journal-title":"Aging Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2235","DOI":"10.1093\/hmg\/ddt612","article-title":"SMN-Dependent Intrinsic Defects in Schwann Cells in Mouse Models of Spinal Muscular Atrophy","volume":"23","author":"Hunter","year":"2014","journal-title":"Human. Mol. Genet."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1093\/hmg\/ddab365","article-title":"Assessment of Cerebral Spinal Fluid Biomarkers and microRNA-Mediated Disease Mechanisms in Spinal Muscular Atrophy Patient Samples","volume":"31","author":"Welby","year":"2022","journal-title":"Human. Mol. Genet."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3409","DOI":"10.1093\/hmg\/ddx230","article-title":"Astrocyte-Produced miR-146a as a Mediator of Motor Neuron Loss in Spinal Muscular Atrophy","volume":"26","author":"Sison","year":"2017","journal-title":"Human. Mol. Genet."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1089\/omi.2018.0106","article-title":"Do Perineuronal Net Elements Contribute to Pathophysiology of Spinal Muscular Atrophy? In Vitro and Transcriptomics Insights","volume":"22","author":"Eskici","year":"2018","journal-title":"OMICS J. Integr. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s00018-023-04885-7","article-title":"Multi-Omics Profiling of CSF from Spinal Muscular Atrophy Type 3 Patients after Nusinersen Treatment: A 2-Year Follow-up Multicenter Retrospective Study","volume":"80","author":"Faravelli","year":"2023","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1111\/jnc.14953","article-title":"Cerebrospinal Fluid Proteomic Profiling in Nusinersen-treated Patients with Spinal Muscular Atrophy","volume":"153","author":"Kessler","year":"2020","journal-title":"J. Neurochem."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Rocha, D.N., Carvalho, E.D., Relvas, J.B., Oliveira, M.J., and P\u00eago, A.P. (2022). Mechanotransduction: Exploring New Therapeutic Avenues in Central Nervous System Pathology. Front. Neurosci., 16.","DOI":"10.3389\/fnins.2022.861613"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/s41392-023-01501-9","article-title":"Cellular Mechanotransduction in Health and Diseases: From Molecular Mechanism to Therapeutic Targets","volume":"8","author":"Di","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1038\/s41593-024-01714-3","article-title":"Astrocytes Require Perineuronal Nets to Maintain Synaptic Homeostasis in Mice","volume":"27","author":"Tewari","year":"2024","journal-title":"Nat. Neurosci."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Tewari, B.P., Chaunsali, L., Prim, C.E., and Sontheimer, H. (2022). A Glial Perspective on the Extracellular Matrix and Perineuronal Net Remodeling in the Central Nervous System. Front. Cell. Neurosci., 16.","DOI":"10.3389\/fncel.2022.1022754"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.neuron.2023.10.005","article-title":"Mechanics in the Nervous System: From Development to Disease","volume":"112","author":"Pillai","year":"2024","journal-title":"Neuron"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Proc\u00e8s, A., Luciano, M., Kalukula, Y., Ris, L., and Gabriele, S. (2022). Multiscale Mechanobiology in Brain Physiology and Diseases. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.823857"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1093\/brain\/awaa420","article-title":"An Ancestral 10-Bp Repeat Expansion in VWA1 Causes Recessive Hereditary Motor Neuropathy","volume":"144","author":"Pagnamenta","year":"2021","journal-title":"Brain"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1093\/brain\/awaa418","article-title":"Bi-Allelic Truncating Mutations in VWA1 Cause Neuromyopathy","volume":"144","author":"Deschauer","year":"2021","journal-title":"Brain"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"fcae377","DOI":"10.1093\/braincomms\/fcae377","article-title":"Autosomal Recessive VWA1-Related Disorder: Comprehensive Analysis of Phenotypic Variability and Genetic Mutations","volume":"6","author":"Nagy","year":"2024","journal-title":"Brain Commun."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"12020","DOI":"10.1074\/jbc.M806968200","article-title":"Mice Lacking the Extracellular Matrix Protein WARP Develop Normally but Have Compromised Peripheral Nerve Structure and Function","volume":"284","author":"Allen","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Zeng, C.-W. (2023). Multipotent Mesenchymal Stem Cell-Based Therapies for Spinal Cord Injury: Current Progress and Future Prospects. 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