{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:06:02Z","timestamp":1791918362033,"version":"4.3.4"},"reference-count":154,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:00:00Z","timestamp":1758672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Universiti Kebangsaan Malaysia (UKM)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Neurodegenerative diseases such as Alzheimer\u2019s disease (AD), Parkinson\u2019s disease (PD), Huntington\u2019s disease, multiple sclerosis, and amyotrophic lateral sclerosis share converging mechanisms of neuronal dysfunction, including protein aggregation, oxidative stress, and chronic neuroinflammation. Glial cells, once considered passive supporters, are now recognized as central drivers of these processes, offering both pathogenic triggers and therapeutic opportunities. Yet, despite compelling preclinical evidence, the translation of glial-targeted therapies into clinical success has been limited. This review provides a critical synthesis of current knowledge by examining therapeutic strategies through the lens of their translational challenges and failures. This narrative review highlights how interspecies variability of glial phenotypes, shifting neuroprotective versus neurotoxic states, limited biomarker stratification, and delivery barriers have constrained trials, such as anti-triggering receptor expressed on myeloid cells 2 (anti-TREM2) antibodies in AD and glial cell line-derived neurotrophic factor (GDNF) in PD. By analyzing these obstacles across major neurodegenerative disorders, this review argue that the next stage of glial medicine requires precision approaches that integrate stage-specific phenotyping, biomarker-guided patient selection, and innovative delivery platforms. Understanding not only what has been tried but why translation has stalled is essential to chart a roadmap for effective, disease-modifying glial therapies in the aging brain.<\/jats:p>","DOI":"10.3390\/cells14191497","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T07:46:49Z","timestamp":1758786409000},"page":"1497","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Glial Cells as Emerging Therapeutic Targets in Neurodegenerative Diseases: Mechanistic Insights and Translational Perspectives"],"prefix":"10.3390","volume":"14","author":[{"given":"Thirupathirao","family":"Vishnumukkala","sequence":"first","affiliation":[{"name":"Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia"},{"name":"Human Biology Department, School of Medicine, IMU University, Bukit Jalil, Kuala Lumpur 57000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2019-4565","authenticated-orcid":false,"given":"Che Mohd Nasril","family":"Che Mohd Nassir","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiology, School of Basic Medical Sciences, Faculty of Medicine, Universiti Sultan Zainal Abidin, Kuala Terengganu 20400, Terengganu, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7621-7132","authenticated-orcid":false,"given":"Zaw Myo","family":"Hein","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine, Ajman University, Ajman P.O. Box 346, United Arab Emirates"},{"name":"Center of Medical and Bio-Allied Health Sciences Research (CMBHSR), Ajman University, Ajman, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prarthana","family":"Kalerammana Gopalakrishna","sequence":"additional","affiliation":[{"name":"Human Biology Department, School of Medicine, IMU University, Bukit Jalil, Kuala Lumpur 57000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barani","family":"Karikalan","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, MAHSA University, Bandar Saujana Putra, Jenjarom 42610, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aisyah","family":"Alkatiri","sequence":"additional","affiliation":[{"name":"Human Biology Department, School of Medicine, IMU University, Bukit Jalil, Kuala Lumpur 57000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saravanan","family":"Jagadeesan","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine, Taylor\u2019s University, Lakeside Campus, Subang Jaya 47500, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3263-1061","authenticated-orcid":false,"given":"Venkatesh R.","family":"Naik","sequence":"additional","affiliation":[{"name":"Department of Preclinical Sciences, Faculty of Medicine and Health Sciences, University Tunku Abdul Rahman, Jalan Sungai Long, Bandar Sungai Long, Kajang 31900, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warren","family":"Thomas","sequence":"additional","affiliation":[{"name":"School of Medicine, Royal College of Surgeons in Ireland\u2014Medical University of Bahrain, Muharraq Governate, Kingdom of Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9282-129X","authenticated-orcid":false,"given":"Mohamad Aris","family":"Mohd Moklas","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4163-2234","authenticated-orcid":false,"given":"Mohd Amir","family":"Kamaruzzaman","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia"},{"name":"Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.cell.2022.12.032","article-title":"Hallmarks of neurodegenerative diseases","volume":"186","author":"Wilson","year":"2023","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"101628","DOI":"10.1016\/j.smim.2022.101628","article-title":"Pathophysiology of neurodegenerative diseases: An interplay among axonal transport failure, oxidative stress, and inflammation?","volume":"59","author":"Tesco","year":"2022","journal-title":"Semin. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.mehy.2018.06.009","article-title":"Garcinol, an effective monoamine oxidase-B inhibitor for the treatment of Parkinson\u2019s disease","volume":"117","author":"Mazumder","year":"2018","journal-title":"Med. Hypotheses"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Adamu, A., Li, S., Gao, F., and Xue, G. (2024). The role of neuroinflammation in neurodegenerative diseases: Current understanding and future therapeutic targets. Front. Aging Neurosci., 16.","DOI":"10.3389\/fnagi.2024.1347987"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1093\/toxsci\/kfr239","article-title":"The role of environmental exposures in neurodegeneration and neurodegenerative diseases","volume":"124","author":"Cannon","year":"2011","journal-title":"Toxicol. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ayeni, E.A., Aldossary, A.M., Ayejoto, D.A., Gbadegesin, L.A., Alshehri, A.A., Alfassam, H.A., Afewerky, H.K., Almughem, F.A., Bello, S.M., and Tawfik, E.A. (2022). Neurodegenerative diseases: Implications of Environmental and Climatic Influences on Neurotransmitters and Neuronal Hormones Activities. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph191912495"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1126\/science.aah4968","article-title":"Mechanisms linking circadian clocks, sleep, and neurodegeneration","volume":"354","author":"Musiek","year":"2016","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1001\/jama.2017.3090","article-title":"Association Between Midlife Vascular Risk Factors and Estimated Brain Amyloid Deposition","volume":"317","author":"Gottesman","year":"2017","journal-title":"JAMA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1038\/s41582-018-0072-1","article-title":"TREM2\u2014A key player in microglial biology and Alzheimer disease","volume":"14","author":"Ulland","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Mendes-Oliveira, J., Campos, F.L., Ferreira, S.A., Tom\u00e9, D., Fonseca, C.P., and Baltazar, G. (2023). Endogenous GDNF Is Unable to Halt Dopaminergic Injury Triggered by Microglial Activation. Cells, 13.","DOI":"10.3390\/cells13010074"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1016\/S1474-4422(14)70222-4","article-title":"Safety and efficacy of ceftriaxone for amyotrophic lateral sclerosis: A multi-stage, randomised, double-blind, placebo-controlled trial","volume":"13","author":"Cudkowicz","year":"2014","journal-title":"Lancet Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"13742","DOI":"10.1523\/JNEUROSCI.4844-08.2008","article-title":"Organization and postembryonic development of glial cells in the adult central brain of Drosophila","volume":"28","author":"Awasaki","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Gao, L., Pan, X., Zhang, J.H., and Xia, Y. (2023). Glial cells: An important switch for the vascular function of the central nervous system. Front. Cell Neurosci., 17.","DOI":"10.3389\/fncel.2023.1166770"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1002\/glia.24336","article-title":"Emerging concepts in oligodendrocyte and myelin formation, inputs from the zebrafish model","volume":"71","author":"Masson","year":"2023","journal-title":"Glia"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1146\/annurev-immunol-051116-052358","article-title":"Microglia Function in the Central Nervous System During Health and Neurodegeneration","volume":"35","author":"Colonna","year":"2017","journal-title":"Annu. Rev. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1177\/1073858413504465","article-title":"Glial biology in learning and cognition","volume":"20","author":"Fields","year":"2014","journal-title":"Neuroscientist"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/s41392-023-01486-5","article-title":"Role of neuroinflammation in neurodegeneration development","volume":"8","author":"Chen","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Singh, A., Kukreti, R., Saso, L., and Kukreti, S. (2019). Oxidative stress: A key modulator in neurodegenerative diseases. Molecules, 24.","DOI":"10.3390\/molecules24081583"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1016\/j.neuron.2017.01.022","article-title":"Autophagy and neurodegeneration: Pathogenic mechanisms and therapeutic opportunities","volume":"93","author":"Menzies","year":"2017","journal-title":"Neuron"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"577232","DOI":"10.1016\/j.jneuroim.2020.577232","article-title":"The induction of Neuron-Glial2 (NG2) expressing cells in methamphetamine toxicity-induced neuroinflammation in rat brain are averted by melatonin","volume":"344","author":"Hein","year":"2020","journal-title":"J. Neuroimmunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nature21029","article-title":"Neurotoxic reactive astrocytes are induced by activated microglia","volume":"541","author":"Liddelow","year":"2017","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"459","DOI":"10.14336\/AD.2023.0718","article-title":"The Role of Glial Cells in Synaptic Dysfunction: Insights into Alzheimer\u2019s Disease Mechanisms","volume":"15","author":"Yu","year":"2024","journal-title":"Aging Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1093\/abbs\/gmv004","article-title":"Glial U87 cells protect neuronal SH-SY5Y cells from indirect effect of radiation by reducing oxidative stress and apoptosis","volume":"47","author":"Saeed","year":"2015","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"541","DOI":"10.2174\/1381612822666151125000300","article-title":"Inflammatory Process in Alzheimer\u2019s and Parkinson\u2019s Diseases: Central Role of Cytokines","volume":"22","author":"Alam","year":"2016","journal-title":"Curr. Pharm. Des."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Di Benedetto, G., Burgaletto, C., Bellanca, C.M., Munaf\u00f2, A., Bernardini, R., and Cantarella, G. (2022). Role of Microglia and Astrocytes in Alzheimer\u2019s Disease: From Neuroinflammation to Ca2+ Homeostasis Dysregulation. Cells, 11.","DOI":"10.3390\/cells11172728"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.brainresbull.2011.10.004","article-title":"Role of pro-inflammatory cytokines released from microglia in neurodegenerative diseases","volume":"87","author":"Smith","year":"2012","journal-title":"Brain Res. Bull."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2546","DOI":"10.1084\/jem.20190980","article-title":"Microglia drive APOE-dependent neurodegeneration in a tauopathy mouse model","volume":"216","author":"Shi","year":"2019","journal-title":"J. Exp. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1016\/j.pain.2013.06.022","article-title":"Glia and pain: Is chronic pain a gliopathy?","volume":"154","author":"Ji","year":"2013","journal-title":"Pain"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e155096","DOI":"10.1172\/JCI155096","article-title":"Sec13 promotes oligodendrocyte differentiation and myelin repair through autocrine pleiotrophin signaling","volume":"132","author":"Liu","year":"2022","journal-title":"J. Clin. Investig."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Kempuraj, D., Thangavel, R., Selvakumar, G.P., Zaheer, S., Ahmed, M.E., Raikwar, S.P., Zahoor, H., Saeed, D., Natteru, P.A., and Iyer, S. (2017). Brain and Peripheral Atypical Inflammatory Mediators Potentiate Neuroinflammation and Neurodegeneration. Front. Cell. Neurosci., 11.","DOI":"10.3389\/fncel.2017.00216"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1038\/nature11729","article-title":"NLRP3 is activated in Alzheimer\u2019s disease and contributes to pathology in APP\/PS1 mice","volume":"493","author":"Heneka","year":"2013","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Wood, O.W.G., Yeung, J.H.Y., Faull, R.L.M., and Kwakowsky, A. (2022). EAAT2 as a therapeutic research target in Alzheimer\u2019s disease: A systematic review. Front. Neurosci., 16.","DOI":"10.3389\/fnins.2022.952096"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.tins.2017.04.001","article-title":"The Role of Astrocyte Dysfunction in Parkinson\u2019s Disease Pathogenesis","volume":"40","author":"Booth","year":"2017","journal-title":"Trends Neurosci."},{"key":"ref_34","first-page":"100395","article-title":"Neuron-Glial2 (NG2) cells: A promising target for neuroinflammation-related neurodegeneration","volume":"39","author":"Hein","year":"2025","journal-title":"Transl. Res. Anat."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1038\/s41591-018-0051-5","article-title":"Block of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson\u2019s disease","volume":"24","author":"Yun","year":"2018","journal-title":"Nat. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.it.2015.04.007","article-title":"The choreography of neuroinflammation in Huntington\u2019s disease","volume":"36","author":"Crotti","year":"2015","journal-title":"Trends Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.stem.2018.11.010","article-title":"Human ESC-Derived Chimeric Mouse Models of Huntington\u2019s Disease Reveal Cell-Intrinsic Defects in Glial Progenitor Cell Differentiation","volume":"24","author":"Osipovitch","year":"2019","journal-title":"Cell Stem Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.jneuroim.2014.06.009","article-title":"Astrocyte CCL2 sustains immune cell infiltration in chronic experimental autoimmune encephalomyelitis","volume":"274","author":"Kim","year":"2014","journal-title":"J. Neuroimmunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1186\/s12974-021-02309-6","article-title":"The semantics of microglia activation: Neuroinflammation, homeostasis, and stress","volume":"18","author":"Woodburn","year":"2021","journal-title":"J Neuroinflammation"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.neuron.2020.08.012","article-title":"Astrocyte Crosstalk in CNS Inflammation","volume":"108","author":"Linnerbauer","year":"2020","journal-title":"Neuron"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nature20413","article-title":"Decoding ALS: From genes to mechanism","volume":"539","author":"Taylor","year":"2016","journal-title":"Nature"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.expneurol.2014.05.015","article-title":"Glial cells in amyotrophic lateral sclerosis","volume":"262 Pt B","author":"Philips","year":"2014","journal-title":"Exp. Neurol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.3233\/JAD-170585","article-title":"Mitochondria and Mitochondrial Cascades in Alzheimer\u2019s Disease","volume":"62","author":"Swerdlow","year":"2018","journal-title":"J. Alzheimers Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1602\/neurorx.2.3.484","article-title":"Toxin-induced models of Parkinson\u2019s disease","volume":"2","author":"Prou","year":"2005","journal-title":"NeuroRx"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1002\/mds.21540","article-title":"Clinical correlates of mitochondrial function in Huntington\u2019s disease muscle","volume":"22","author":"Turner","year":"2007","journal-title":"Mov. Disord."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S1474-4422(14)70256-X","article-title":"Pathological mechanisms in progressive multiple sclerosis","volume":"14","author":"Mahad","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_47","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. Primers"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Wang, T., Sun, Y., and Dettmer, U. (2023). Astrocytes in Parkinson\u2019s Disease: From Role to Possible Intervention. Cells, 12.","DOI":"10.3390\/cells12192336"},{"key":"ref_49","first-page":"E1926","article-title":"\u03b1-Synuclein, a chemoattractant, directs microglial migration via H2O2-mediated Lyn phosphorylation","volume":"112","author":"Wang","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.neuroscience.2011.08.052","article-title":"Pathophysiology of Huntington\u2019s disease: Time-dependent alterations in synaptic and receptor function","volume":"198","author":"Raymond","year":"2011","journal-title":"Neuroscience"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"eaaw8546","DOI":"10.1126\/scitranslmed.aaw8546","article-title":"Astrocyte molecular signatures in Huntington\u2019s disease","volume":"11","author":"Gangwani","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/nrn2480","article-title":"Remyelination in the CNS: From biology to therapy","volume":"9","author":"Franklin","year":"2008","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_53","first-page":"188","article-title":"Promoting oligodendrocyte precursor cell maturation and proliferation for remyelination in multiple sclerosis","volume":"47","author":"Franco","year":"2015","journal-title":"Brain Behav. Immun."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/S0896-6273(00)80086-0","article-title":"Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate","volume":"16","author":"Rothstein","year":"1996","journal-title":"Neuron"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1038\/s41573-022-00390-x","article-title":"Function and therapeutic value of astrocytes in neurological diseases","volume":"21","author":"Lee","year":"2022","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Hemonnot, A.L., Hua, J., Ulmann, L., and Hirbec, H. (2019). Microglia in Alzheimer Disease: Well-Known Targets and New Opportunities. Front. Aging Neurosci., 11.","DOI":"10.3389\/fnagi.2019.00233"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"9262","DOI":"10.1074\/jbc.M109.081125","article-title":"Direct transfer of alpha-synuclein from neuron to astroglia causes inflammatory responses in synucleinopathies","volume":"285","author":"Lee","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"578222","DOI":"10.1016\/j.jneuroim.2023.578222","article-title":"Plasma TNF-\u03b1 and phosphorylated \u03b1-syn are associated with fatigue in patients with Parkinson\u2019s disease","volume":"385","author":"Wang","year":"2023","journal-title":"J. Neuroimmunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"S9","DOI":"10.1016\/j.parkreldis.2004.10.013","article-title":"Neuroinflammatory processes in Parkinson\u2019s disease","volume":"11","author":"Hirsch","year":"2005","journal-title":"Park. Relat. Disord."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.tig.2004.01.008","article-title":"Huntingtin-protein interactions and the pathogenesis of Huntington\u2019s disease","volume":"20","author":"Li","year":"2004","journal-title":"Trends Genet."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Palpagama, T.H., Waldvogel, H.J., Faull, R.L.M., and Kwakowsky, A. (2019). The Role of Microglia and Astrocytes in Huntington\u2019s Disease. Front. Mol. Neurosci., 12.","DOI":"10.3389\/fnmol.2019.00258"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Mado, H., Adamczyk-Sowa, M., and Sowa, P. (2023). Role of Microglial Cells in the Pathophysiology of MS: Synergistic or Antagonistic?. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24031861"},{"key":"ref_63","first-page":"248ra104","article-title":"Genetic validation of a therapeutic target in a mouse model of ALS","volume":"6","author":"Koszka","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1093\/brain\/awx118","article-title":"Clinical criteria for subtyping Parkinson\u2019s disease: Biomarkers and longitudinal progression","volume":"140","author":"Fereshtehnejad","year":"2017","journal-title":"Brain"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1007\/s12272-024-01499-w","article-title":"Exploring molecular mechanisms, therapeutic strategies, and clinical manifestations of Huntington\u2019s disease","volume":"47","author":"Shafie","year":"2024","journal-title":"Arch. Pharm. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1056\/NEJMoa1110740","article-title":"Potassium channel KIR4.1 as an immune target in multiple sclerosis","volume":"367","author":"Srivastava","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1089\/neu.2010.1626","article-title":"Transplantation of human glial restricted progenitors and derived astrocytes into a contusion model of spinal cord injury","volume":"28","author":"Jin","year":"2011","journal-title":"J. Neurotrauma"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1097\/00019052-200108000-00009","article-title":"The role of glial cells in Parkinson\u2019s disease","volume":"14","author":"Vila","year":"2021","journal-title":"Curr. Opin. Neurol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.4103\/1673-5374.387967","article-title":"\u03b1-Synuclein pathology from the body to the brain: So many seeds so close to the central soil","volume":"19","author":"Yang","year":"2024","journal-title":"Neural Regen. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"15005","DOI":"10.1038\/nrdp.2015.5","article-title":"Huntington disease","volume":"1","author":"Bates","year":"2015","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e1169","DOI":"10.1002\/ctm2.1169","article-title":"Conclusions of the SIGNAL study in Huntington and implications for treatment of other slowly progressive neurodegenerative diseases","volume":"13","author":"Zauderer","year":"2023","journal-title":"Clin. Transl. Med."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Heffernan, C., Sumer, H., Guillemin, G.J., Manuelpillai, U., and Verma, P.J. (2012). Design and screening of a glial cell-specific, cell penetrating peptide for therapeutic applications in multiple sclerosis. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0045501"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"380","DOI":"10.4252\/wjsc.v7.i2.380","article-title":"Transplantation of stem cell-derived astrocytes for the treatment of amyotrophic lateral sclerosis and spinal cord injury","volume":"7","author":"Nicaise","year":"2015","journal-title":"World J. Stem Cells."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1111\/j.1471-4159.2012.07664.x","article-title":"Glial cells in (patho)physiology","volume":"121","author":"Parpura","year":"2012","journal-title":"J. Neurochem."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Hein, Z.M., Vishnumukkala, T., Karikalan, B., Alkatiri, A., Hussan, F., Jagadeesan, S., Kamaruzzaman, M.A., Che Ramli, M.D., Che Mohd Nassir, C.M.N., and Gopalakrishna, P.K. (2025). Autophagy and Alzheimer\u2019s Disease: Mechanisms and Impact Beyond the Brain. Cells, 14.","DOI":"10.3390\/cells14120911"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Silva, M.V.F., Loures, C.M.G., Alves, L.C.V., de Souza, L.C., Borges, K.B.G., and Carvalho, M.D.G. (2019). Alzheimer\u2019s disease: Risk factors and potentially protective measures. J. Biomed. Sci., 26.","DOI":"10.1186\/s12929-019-0524-y"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/ene.13439","article-title":"Alzheimer\u2019s disease","volume":"25","author":"Lane","year":"2018","journal-title":"Eur. J. Neurol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"595","DOI":"10.15252\/emmm.201606210","article-title":"The amyloid hypothesis of Alzheimer\u2019s disease at 25 years","volume":"8","author":"Selkoe","year":"2016","journal-title":"EMBO Mol. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/S1474-4422(15)70016-5","article-title":"Neuroinflammation in Alzheimer\u2019s disease","volume":"14","author":"Heneka","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s13024-019-0333-5","article-title":"The neuropathological diagnosis of Alzheimer\u2019s disease","volume":"14","author":"DeTure","year":"2019","journal-title":"Mol. Neurodegener."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1179573520907397","DOI":"10.1177\/1179573520907397","article-title":"Current and Future Treatments in Alzheimer Disease: An Update","volume":"12","author":"Yiannopoulou","year":"2020","journal-title":"J. Cent. Nerv. Syst. Dis."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/s41582-020-00435-y","article-title":"Neuroinflammation and microglial activation in Alzheimer disease: Where do we go from here?","volume":"17","author":"Leng","year":"2021","journal-title":"Nat. Rev. Neurol."},{"key":"ref_83","first-page":"43","article-title":"Alzheimer\u2019s Disease Puzzle: Delving into Pathogenesis Hypotheses","volume":"15","author":"Nasb","year":"2024","journal-title":"Aging Dis."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"S567","DOI":"10.3233\/JAD-179941","article-title":"The Amyloid-\u03b2 Oligomer Hypothesis: Beginning of the Third Decade","volume":"64","author":"Cline","year":"2018","journal-title":"J. Alzheimers Dis."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/nrneurol.2015.225","article-title":"Tau and neurodegenerative disease: The story so far","volume":"12","author":"Iqbal","year":"2016","journal-title":"Nat. Rev. Neurol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/BF00308809","article-title":"Neuropathological stageing of Alzheimer-related changes","volume":"82","author":"Braak","year":"1991","journal-title":"Acta Neuropathol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1038\/nn.2583","article-title":"Amyloid-beta-induced neuronal dysfunction in Alzheimer\u2019s disease: From synapses toward neural networks","volume":"13","author":"Palop","year":"2010","journal-title":"Nat. Neurosci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/nrneurol.2017.188","article-title":"Blood-brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders","volume":"14","author":"Sweeney","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1586\/14737175.8.11.1703","article-title":"Cholinergic system during the progression of Alzheimer\u2019s disease: Therapeutic implications","volume":"8","author":"Mufson","year":"2008","journal-title":"Expert. Rev. Neurother."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1212\/WNL.0000000000000596","article-title":"Symptom onset in autosomal dominant Alzheimer disease: A systematic review and meta-analysis","volume":"83","author":"Ryman","year":"2014","journal-title":"Neurology"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.neuron.2009.06.026","article-title":"The role of apolipoprotein E in Alzheimer\u2019s disease","volume":"63","author":"Kim","year":"2009","journal-title":"Neuron"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.neuron.2015.11.013","article-title":"Purification and characterization of progenitor and mature human astrocytes reveals transcriptional and functional differences with mouse","volume":"89","author":"Zhang","year":"2016","journal-title":"Neuron"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Wang, C., Zong, S., Cui, X., Wang, X., Wu, S., Wang, L., Liu, Y., and Lu, Z. (2023). The effects of microglia-associated neuroinflammation on Alzheimer\u2019s disease. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1117172"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1002\/alz.13699","article-title":"Microglia measured by TSPO PET are associated with Alzheimer\u2019s disease pathology and mediate key steps in a disease progression model","volume":"20","author":"Rossano","year":"2024","journal-title":"Alzheimers Dement."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1093\/brain\/awv379","article-title":"Pharmacological targeting of CSF1R inhibits microglial proliferation and prevents the progression of Alzheimer\u2019s-like pathology","volume":"139","author":"Schetters","year":"2016","journal-title":"Brain"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"17013","DOI":"10.1038\/nrdp.2017.13","article-title":"Parkinson disease","volume":"3","author":"Poewe","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_97","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_98","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S0197-4580(02)00065-9","article-title":"Staging of brain pathology related to sporadic Parkinson\u2019s disease","volume":"24","author":"Braak","year":"2003","journal-title":"Neurobiol. Aging"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s00441-017-2706-9","article-title":"Neurodegeneration and the ordered assembly of \u03b1-synuclein","volume":"373","author":"Spillantini","year":"2018","journal-title":"Cell Tissue Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/S0140-6736(14)61393-3","article-title":"Parkinson\u2019s disease","volume":"386","author":"Kalia","year":"2015","journal-title":"Lancet"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.parkreldis.2019.03.026","article-title":"Orally inhaled levodopa (CVT-301) for early morning OFF periods in Parkinson\u2019s disease","volume":"64","author":"Hauser","year":"2019","journal-title":"Park. Relat. Disord."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nrn.2016.178","article-title":"Selective neuronal vulnerability in Parkinson disease","volume":"18","author":"Surmeier","year":"2017","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1038\/nrn2915","article-title":"Goal-directed and habitual control in the basal ganglia: Implications for Parkinson\u2019s disease","volume":"11","author":"Redgrave","year":"2010","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1136\/jnnp.55.3.181","article-title":"Accuracy of clinical diagnosis of idiopathic Parkinson\u2019s disease: A clinico-pathological study of 100 cases","volume":"55","author":"Hughes","year":"1992","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Zhang, X., Zhang, R., Nisa Awan, M.U., and Bai, J. (2022). The Mechanism and Function of Glia in Parkinson\u2019s Disease. Front. Cell Neurosci., 16.","DOI":"10.3389\/fncel.2022.903469"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"S55","DOI":"10.1002\/mds.22638","article-title":"Inflammation and Parkinson\u2019s disease pathogenesis","volume":"25","author":"Przedborski","year":"2010","journal-title":"Mov. Disord."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/s12974-021-02132-z","article-title":"The CD200R1 microglial inhibitory receptor as a therapeutic target in the MPTP model of Parkinson\u2019s disease","volume":"18","author":"Serratosa","year":"2021","journal-title":"J. Neuroinflammation"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1093\/brain\/awz023","article-title":"Randomized trial of intermittent intraputamenal glial cell line-derived neurotrophic factor in Parkinson\u2019s disease","volume":"142","author":"Whone","year":"2019","journal-title":"Brain"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1111\/j.1471-4159.2011.07272.x","article-title":"Neuroprotective properties of marrow-isolated adult multilineage-inducible cells in rat hippocampus following global cerebral ischemia are enhanced when complexed to biomimetic microcarriers","volume":"119","author":"Garbayo","year":"2011","journal-title":"J. Neurochem."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Rabaneda-Lombarte, N., Blasco-Agell, L., Serratosa, J., Ferigle, L., Saura, J., and Sol\u00e0, C. (2020). Parkinsonian neurotoxicants impair the anti-inflammatory response induced by IL4 in glial cells: Involvement of the CD200-CD200R1 ligand-receptor pair. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-67649-4"},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Olsen, A.L., and Feany, M.B. (2021). Parkinson\u2019s disease risk genes act in glia to control neuronal \u03b1-synuclein toxicity. Neurobiol. Dis., 159.","DOI":"10.1016\/j.nbd.2021.105482"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Montalb\u00e1n-Rodr\u00edguez, A., Abalo, R., and L\u00f3pez-G\u00f3mez, L. (2024). From the Gut to the Brain: The Role of Enteric Glial Cells and Their Involvement in the Pathogenesis of Parkinson\u2019s Disease. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25021294"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1111\/jnc.12742","article-title":"Enteric GFAP expression and phosphorylation in Parkinson\u2019s disease","volume":"130","author":"Clairembault","year":"2014","journal-title":"J. Neurochem."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1038\/s41467-020-15119-w","article-title":"Microglia clear neuron-released \u03b1-synuclein via selective autophagy and prevent neurodegeneration","volume":"11","author":"Choi","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_115","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_116","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s40478-015-0196-0","article-title":"Structural alterations of the intestinal epithelial barrier in Parkinson\u2019s disease","volume":"3","author":"Clairembault","year":"2015","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_117","first-page":"301","article-title":"Extended Treatment with Glial Cell Line-Derived Neurotrophic Factor in Parkinson\u2019s Disease","volume":"9","author":"Whone","year":"2019","journal-title":"J. Park. Dis."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/S0140-6736(07)60111-1","article-title":"Huntington\u2019s disease","volume":"369","author":"Walker","year":"2007","journal-title":"Lancet"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2327","DOI":"10.1002\/mds.29228","article-title":"Prevalence and Incidence of Huntington\u2019s Disease: An Updated Systematic Review and Meta-Analysis","volume":"37","author":"Medina","year":"2022","journal-title":"Mov. Disord."},{"key":"ref_120","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_121","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1111\/bpa.12426","article-title":"Huntington\u2019s disease (HD): The neuropathology of a multisystem neurodegenerative disorder of the human brain","volume":"26","author":"Seidel","year":"2016","journal-title":"Brain Pathol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S1474-4422(10)70245-3","article-title":"Huntington\u2019s disease: From molecular pathogenesis to clinical treatment","volume":"10","author":"Ross","year":"2011","journal-title":"Lancet Neurol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1038\/s41582-020-0389-4","article-title":"Huntington disease: New insights into molecular pathogenesis and therapeutic opportunities","volume":"16","author":"Tabrizi","year":"2020","journal-title":"Nat. Rev. Neurol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1152\/physrev.00041.2009","article-title":"Molecular mechanisms and potential therapeutical targets in Huntington\u2019s disease","volume":"90","author":"Zuccato","year":"2010","journal-title":"Physiol. Rev."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1007\/s13311-012-0112-2","article-title":"Huntington\u2019s disease and the striatal medium spiny neuron: Cell-autonomous and non-cell-autonomous mechanisms of disease","volume":"9","author":"Ehrlich","year":"2012","journal-title":"Neurotherapeutics"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1002\/ana.26753","article-title":"Microglial and Astrocytic Responses in the Human Midcingulate Cortex in Huntington\u2019s Disease","volume":"94","author":"Palpagama","year":"2023","journal-title":"Ann. Neurol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"11758","DOI":"10.1038\/ncomms11758","article-title":"Human glia can both induce and rescue aspects of disease phenotype in Huntington disease","volume":"7","author":"Benraiss","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Perucho, J., Casarejos, M.J., G\u00f3mez, A., Ru\u00edz, C., Fern\u00e1ndez-Estevez, M.\u00c1., Mu\u00f1oz, M.P., de Y\u00e9benes, J.G., and Mena, M.\u00c1. (2013). Striatal infusion of glial conditioned medium diminishes huntingtin pathology in r6\/1 mice. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0073120"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.stem.2012.04.026","article-title":"Genetic correction of Huntington\u2019s disease phenotypes in induced pluripotent stem cells","volume":"11","author":"An","year":"2012","journal-title":"Cell Stem Cell"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"e37297","DOI":"10.1097\/MD.0000000000037297","article-title":"Review of multiple sclerosis: Epidemiology, etiology, pathophysiology, and treatment","volume":"103","author":"Haki","year":"2024","journal-title":"Medicine"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1586\/14737175.2013.865866","article-title":"Environmental factors in multiple sclerosis","volume":"13","author":"Ascherio","year":"2013","journal-title":"Expert. Rev. Neurother."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/nrneurol.2012.168","article-title":"Progressive multiple sclerosis: Pathology and pathogenesis","volume":"8","author":"Lassmann","year":"2012","journal-title":"Nat. Rev. Neurol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1016\/S0140-6736(18)30481-1","article-title":"Multiple sclerosis","volume":"391","author":"Thompson","year":"2018","journal-title":"Lancet"},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Pogoda-Weso\u0142owska, A., Dziedzic, A., Maciak, K., St\u0229pie\u0144, A., Dziaduch, M., and Saluk, J. (2023). Neurodegeneration and its potential markers in the diagnosing of secondary progressive multiple sclerosis. A review. Front. Mol. Neurosci., 16.","DOI":"10.3389\/fnmol.2023.1210091"},{"key":"ref_135","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_136","doi-asserted-by":"crossref","first-page":"e1854","DOI":"10.1212\/WNL.0000000000010376","article-title":"Five years of ocrelizumab in relapsing multiple sclerosis: OPERA studies open-label extension","volume":"95","author":"Hauser","year":"2020","journal-title":"Neurology"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/nrneurol.2016.187","article-title":"Interactions between genetic, lifestyle and environmental risk factors for multiple sclerosis","volume":"13","author":"Olsson","year":"2017","journal-title":"Nat. Rev. Neurol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.arcmed.2014.11.013","article-title":"Role of the blood-brain barrier in multiple sclerosis","volume":"45","author":"Ortiz","year":"2014","journal-title":"Arch. Med. Res."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1002\/glia.23556","article-title":"The formation of a glial scar does not prohibit remyelination in an animal model of multiple sclerosis","volume":"67","author":"Haindl","year":"2019","journal-title":"Glia"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"e20202715","DOI":"10.1084\/jem.20202715","article-title":"Functional immune cell-astrocyte interactions","volume":"218","author":"Sanmarco","year":"2021","journal-title":"J. Exp. Med."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1038\/nm.3681","article-title":"Regulation of astrocyte activation by glycolipids drives chronic CNS inflammation","volume":"20","author":"Mayo","year":"2014","journal-title":"Nat. Med."},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Barriola, S., P\u00e9rez-Cerd\u00e1, F., Matute, C., Bribi\u00e1n, A., and L\u00f3pez-Mascaraque, L. (2020). A Clonal NG2-Glia Cell Response in a Mouse Model of Multiple Sclerosis. Cells, 9.","DOI":"10.3390\/cells9051279"},{"key":"ref_143","first-page":"1103","article-title":"Modeling Neuroinflammatory Conditions and Remyelination Using iPSC Derived Glial Cells","volume":"10","author":"Zheng","year":"2018","journal-title":"Stem Cell Rep."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Theophanous, S., Sargiannidou, I., and Kleopa, K.A. (2024). Glial Cells as Key Regulators in Neuroinflammatory Mechanisms Associated with Multiple Sclerosis. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25179588"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/nrn3898","article-title":"Astrocyte barriers to neurotoxic inflammation","volume":"16","author":"Sofroniew","year":"2015","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1101\/gad.1806309","article-title":"Dysregulation of the Wnt Pathway Inhibits Timely Myelination and Remyelination in the Mammalian Central Nervous System","volume":"23","author":"Fancy","year":"2009","journal-title":"Genes Dev."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1159\/000351153","article-title":"Global epidemiology of amyotrophic lateral sclerosis: A systematic review of published literature","volume":"41","author":"Logroscino","year":"2013","journal-title":"Neuroepidemiology"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1056\/NEJMra1603471","article-title":"Amyotrophic Lateral Sclerosis","volume":"377","author":"Brown","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.nbd.2017.02.004","article-title":"Neurobiology of axonal transport defects in motor neuron diseases: Opportunities for translational research?","volume":"105","author":"Hafezparast","year":"2017","journal-title":"Neurobiol. Dis."},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Bowerman, M., Vincent, T., Scamps, F., Camu, W., and Raoul, C. (2013). The Neuroinflammation in the Physiopathology of Amyotrophic Lateral Sclerosis. Current Advances in Amyotrophic Lateral Sclerosis, IntechOpen.","DOI":"10.5772\/56489"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1038\/nbt.1957","article-title":"Astrocytes from familial and sporadic ALS patients are toxic to motor neurons","volume":"29","author":"Hester","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"ref_152","first-page":"343","article-title":"Neural and glial progenitor transplantation as a neuroprotective strategy for Amyotrophic Lateral Sclerosis (ALS)","volume":"1628 Pt B","author":"Maragakis","year":"2015","journal-title":"Brain Res."},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Martin-Estebane, M., and Gomez-Nicola, D. (2020). Targeting Microglial Population Dynamics in Alzheimer\u2019s Disease: Are We Ready for a Potential Impact on Immune Function?. Front. Cell. Neurosci., 14.","DOI":"10.3389\/fncel.2020.00149"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.stem.2013.12.001","article-title":"In vivo direct reprogramming of reactive glial cells into functional neurons after brain injury and in an Alzheimer\u2019s disease model","volume":"14","author":"Guo","year":"2014","journal-title":"Cell Stem Cell"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/19\/1497\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:49:08Z","timestamp":1760035748000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/19\/1497"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,24]]},"references-count":154,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["cells14191497"],"URL":"https:\/\/doi.org\/10.3390\/cells14191497","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,24]]}}}