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This review synthesizes emerging innovations in neurotheranostics\u2014integrated diagnostic and therapeutic platforms\u2014focusing on the neurovascular unit (NVU) as a central pathogenic driver and target. Evidence indicates that NVU and BBB dysfunction are early events in Alzheimer\u2019s, Parkinson\u2019s, amyotrophic lateral sclerosis, and Huntington\u2019s diseases, often preceding classic neuropathological hallmarks. The review highlights the potential of nanotechnology, engineered nanoparticles (NPs) and microRNAs (miRNAs) as precision tools for early detection and targeted CNS delivery. Additionally, it discusses the transformative impact of artificial intelligence (AI) in facilitating personalized, predictive care. Transitioning from a generic \u201cone-pill-for-one-disease\u201d model to a patient-centered strategy targeting early NVU alterations is essential. Integrating AI, nanotechnology and NVU-focused strategies offers a promising path toward effective, personalized disease-modifying therapies.<\/jats:p>","DOI":"10.3390\/ijms27167165","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T08:09:36Z","timestamp":1786435776000},"page":"7165","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Theranostic Innovative Strategies for Brain Diseases: New Insights on Neurovascular Unit-Associated Pathological Changes in Neurodegenerative Disorders and Aging"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6936-3852","authenticated-orcid":false,"given":"Giulia","family":"Terribile","sequence":"first","affiliation":[{"name":"School of Medicine and Surgery, University of Milano-Bicocca, Via Cadore 48, 20900 Monza, Italy"},{"name":"Milan Centre for Neuroscience (NeuroMI), University of Milano-Bicocca, 20126 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1016-8424","authenticated-orcid":false,"given":"Matilda","family":"Pedrinazzi","sequence":"additional","affiliation":[{"name":"School of Medicine and Surgery, University of Milano-Bicocca, Via Cadore 48, 20900 Monza, Italy"},{"name":"PhD Program in Neuroscience, University of Milano-Bicocca, Via Cadore 48, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7527-5554","authenticated-orcid":false,"given":"Irene","family":"Frigerio","sequence":"additional","affiliation":[{"name":"School of Medicine and Surgery, University of Milano-Bicocca, Via Cadore 48, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2567-109X","authenticated-orcid":false,"given":"Giulio","family":"Sancini","sequence":"additional","affiliation":[{"name":"School of Medicine and Surgery, University of Milano-Bicocca, Via Cadore 48, 20900 Monza, Italy"},{"name":"Milan Centre for Neuroscience (NeuroMI), University of Milano-Bicocca, 20126 Milan, Italy"},{"name":"NanoMedicine Center (NANOMIB), University of Milano-Bicocca, 20126 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1742-6078","authenticated-orcid":false,"given":"Romina","family":"Combi","sequence":"additional","affiliation":[{"name":"School of Medicine and Surgery, University of Milano-Bicocca, Via Cadore 48, 20900 Monza, Italy"},{"name":"Milan Centre for Neuroscience (NeuroMI), University of Milano-Bicocca, 20126 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1021\/bc200151q","article-title":"Theranostics: Combining imaging and therapy","volume":"22","author":"Kelkar","year":"2011","journal-title":"Bioconjug. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"103085","DOI":"10.1016\/j.arcmed.2024.103085","article-title":"Theranostics Advances in the Treatment and Diagnosis of Neurological and Neurosurgical Diseases","volume":"56","author":"Awuah","year":"2025","journal-title":"Arch. Med. Res."},{"key":"ref_3","first-page":"2937","article-title":"The Expanding Burden of Neurodegenerative Diseases: An Unmet Medical and Social Need","volume":"16","author":"Wang","year":"2024","journal-title":"Aging Dis."},{"key":"ref_4","first-page":"S3","article-title":"The Emerging Evidence of the Parkinson Pandemic","volume":"8","author":"Dorsey","year":"2018","journal-title":"J. Park. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1016\/S0140-6736(24)00757-8","article-title":"Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990-2021: A systematic analysis for the Global Burden of Disease Study 2021","volume":"403","author":"Collaborators","year":"2024","journal-title":"Lancet"},{"key":"ref_6","first-page":"2953","article-title":"The Impact of Aging on Neurological Diseases in the Elderly: Molecular Mechanisms and Therapeutic Perspectives","volume":"16","author":"Zhou","year":"2024","journal-title":"Aging Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.tins.2018.04.005","article-title":"Tracing Environmental Exposure from Neurodevelopment to Neurodegeneration","volume":"41","author":"Heffernan","year":"2018","journal-title":"Trends Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1002\/ana.26897","article-title":"Role of the Exposome in Neurodegenerative Disease: Recent Insights and Future Directions","volume":"95","author":"Sakowski","year":"2024","journal-title":"Ann. Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Uchmanowicz, D., Styszko, K., Chen, X., Terribile, G., Jakhar, R., Sancini, G., and Pyssa, J. (2025). Microplastics in Airborne Particulate Matter: A Comprehensive Review of Separation Techniques, In Vitro Toxicity and Health Impacts. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262110332"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Giammona, A., Terribile, G., Rainone, P., Pellizzer, C., Porro, D., Cerasa, A., Sancini, G., Rashid, A.U., Belloli, S., and Valtorta, S. (2025). Effects of particulate air pollution exposure on lung-brain axis and related miRNAs modulation in mouse models. Front. Cell Dev. Biol., 13.","DOI":"10.3389\/fcell.2025.1526424"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/s12987-024-00563-3","article-title":"Blood-brain barrier disruption: A culprit of cognitive decline?","volume":"21","author":"Che","year":"2024","journal-title":"Fluids Barriers CNS"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Aus\u00f3, E., G\u00f3mez-Vicente, V., and Esquiva, G. (2020). Biomarkers for Alzheimer\u2019s Disease Early Diagnosis. J. Pers. Med., 10.","DOI":"10.3390\/jpm10030114"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.tips.2025.03.006","article-title":"Monitoring neurodegeneration through brain-derived extracellular vesicles in biofluids","volume":"46","author":"Torrini","year":"2025","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/s12987-020-00230-3","article-title":"A blood-brain barrier overview on structure, function, impairment, and biomarkers of integrity","volume":"17","author":"Kadry","year":"2020","journal-title":"Fluids Barriers CNS"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1080\/17435889.2024.2380241","article-title":"Nanoparticles crossing blood-brain barrier need specific design for normal, neurodegenerative or cancerous brain conditions","volume":"19","author":"Ljubimova","year":"2024","journal-title":"Nanomedicine"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.addr.2018.10.011","article-title":"Neurotheranostics as personalized medicines","volume":"148","author":"Kevadiya","year":"2019","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"114426","DOI":"10.1016\/j.jconrel.2025.114426","article-title":"Clinical translation of nanomedicines for brain diseases: Current challenges and future directions","volume":"389","author":"Wang","year":"2025","journal-title":"J. Control Release"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1186\/s12951-025-03415-w","article-title":"Advances in brain-targeted delivery strategies and natural product-mediated enhancement of blood-brain barrier permeability","volume":"23","author":"Liu","year":"2025","journal-title":"J. Nanobiotechnol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1074\/jbc.R116.760215","article-title":"The Translational Significance of the Neurovascular Unit","volume":"292","author":"McConnell","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Wang, L., Han, L., and Liu, S. (2026). Dysfunction of the neurovascular unit as a temporal driver in Alzheimer\u2019s pathogenesis. Transl. Neurodegener., 15.","DOI":"10.1186\/s40035-026-00548-2"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"106028","DOI":"10.1016\/j.nbd.2023.106028","article-title":"How does neurovascular unit dysfunction contribute to multiple sclerosis?","volume":"178","author":"Cashion","year":"2023","journal-title":"Neurobiol. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Gowdy, J., Ahn, J., Miller, R.H., and Islam, Y. (2026). Neurovascular dysfunction in the development and progression of neuroinflammatory diseases. Front. Cell Neurosci., 20.","DOI":"10.3389\/fncel.2026.1741928"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41591-018-0297-y","article-title":"Blood-brain barrier breakdown is an early biomarker of human cognitive dysfunction","volume":"25","author":"Nation","year":"2019","journal-title":"Nat. Med."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Soto-Rojas, L.O., Pacheco-Herrero, M., Mart\u00ednez-G\u00f3mez, P.A., Campa-C\u00f3rdoba, B.B., Ap\u00e1tiga-P\u00e9rez, R., Villegas-Rojas, M.M., Harrington, C.R., de la Cruz, F., Garc\u00e9s-Ram\u00edrez, L., and Luna-Mu\u00f1oz, J. (2021). The Neurovascular Unit Dysfunction in Alzheimer\u2019s Disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22042022"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2824","DOI":"10.1007\/s12035-021-02299-9","article-title":"Multifunctional Liposomes Modulate Purinergic Receptor-Induced Calcium Wave in Cerebral Microvascular Endothelial Cells and Astrocytes: New Insights for Alzheimer\u2019s disease","volume":"58","author":"Forcaia","year":"2021","journal-title":"Mol. Neurobiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/nrn3114","article-title":"Neurovascular pathways to neurodegeneration in Alzheimer\u2019s disease and other disorders","volume":"12","author":"Zlokovic","year":"2011","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"103503","DOI":"10.1016\/j.ebiom.2021.103503","article-title":"Reversing pathology in a preclinical model of Alzheimer\u2019s disease by hacking cerebrovascular neoangiogenesis with advanced cancer therapeutics","volume":"71","author":"Singh","year":"2021","journal-title":"EBioMedicine"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1148\/radiol.2016152244","article-title":"Blood-Brain Barrier Leakage in Patients with Early Alzheimer Disease","volume":"281","author":"Burgmans","year":"2016","journal-title":"Radiology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1111\/jnc.13122","article-title":"A\u03b2(1-42) oligomer-induced leakage in an in vitro blood-brain barrier model is associated with up-regulation of RAGE and metalloproteinases, and down-regulation of tight junction scaffold proteins","volume":"134","author":"Wan","year":"2015","journal-title":"J. Neurochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/S1474-4422(09)70016-X","article-title":"Matrix metalloproteinases and their multiple roles in neurodegenerative diseases","volume":"8","author":"Rosenberg","year":"2009","journal-title":"Lancet Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1159\/000334916","article-title":"Neuroinflammation and blood-brain barrier changes in capillary amyloid angiopathy","volume":"10","author":"Carrano","year":"2012","journal-title":"Neurodegener. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"8845","DOI":"10.1523\/JNEUROSCI.6102-11.2012","article-title":"A\u03b21\u201342-RAGE interaction disrupts tight junctions of the blood-brain barrier via Ca2+-calcineurin signaling","volume":"32","author":"Kook","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e1500472","DOI":"10.1126\/sciadv.1500472","article-title":"Autoregulated paracellular clearance of amyloid-\u03b2 across the blood-brain barrier","volume":"1","author":"Keaney","year":"2015","journal-title":"Sci. Adv."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.neuroimage.2018.09.030","article-title":"Water-exchange MRI detects subtle blood-brain barrier breakdown in Alzheimer\u2019s disease rats","volume":"184","author":"Dickie","year":"2019","journal-title":"Neuroimage"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.neulet.2006.03.047","article-title":"Amyloid beta-peptide1-42 alters tight junction protein distribution and expression in brain microvessel endothelial cells","volume":"401","author":"Marco","year":"2006","journal-title":"Neurosci. Lett."},{"key":"ref_36","first-page":"1101","article-title":"Amyloid-beta-induced occludin down-regulation and increased permeability in human brain endothelial cells is mediated by MAPK activation","volume":"14","author":"Tai","year":"2010","journal-title":"J. Cell Mol. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/nm890","article-title":"RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain","volume":"9","author":"Deane","year":"2003","journal-title":"Nat. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2243","DOI":"10.1038\/s41467-024-46630-z","article-title":"A single nuclear transcriptomic characterisation of mechanisms responsible for impaired angiogenesis and blood-brain barrier function in Alzheimer\u2019s disease","volume":"15","author":"Tsartsalis","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/jcbfm.2015.44","article-title":"Accelerated pericyte degeneration and blood-brain barrier breakdown in apolipoprotein E4 carriers with Alzheimer\u2019s disease","volume":"36","author":"Halliday","year":"2016","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.neulet.2015.09.025","article-title":"Shedding of soluble platelet-derived growth factor receptor-\u03b2 from human brain pericytes","volume":"607","author":"Sagare","year":"2015","journal-title":"Neurosci. Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3816","DOI":"10.1038\/s41467-018-06301-2","article-title":"Apo\u03b54 disrupts neurovascular regulation and undermines white matter integrity and cognitive function","volume":"9","author":"Koizumi","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Li, Y.Y., Guo, D.D., Duan, R.N., and Li, Y. (2024). Interactions between Beta-Amyloid and Pericytes in Alzheimer\u2019s Disease. Front. Biosci. (Landmark Ed.), 29.","DOI":"10.31083\/j.fbl2904136"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1152\/physrev.00050.2017","article-title":"Blood-Brain Barrier: From Physiology to Disease and Back","volume":"99","author":"Sweeney","year":"2019","journal-title":"Physiol. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/978-981-13-9913-8_11","article-title":"Astroglia in Alzheimer\u2019s Disease","volume":"1175","author":"Verkhratsky","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1001\/jamaneurol.2016.4370","article-title":"Association of Perivascular Localization of Aquaporin-4 With Cognition and Alzheimer Disease in Aging Brains","volume":"74","author":"Zeppenfeld","year":"2017","journal-title":"JAMA Neurol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Gratuze, M., Chen, Y., Parhizkar, S., Jain, N., Strickland, M.R., Serrano, J.R., Colonna, M., Ulrich, J.D., and Holtzman, D.M. (2021). Activated microglia mitigate A\u03b2-associated tau seeding and spreading. J. Exp. Med., 218.","DOI":"10.1084\/jem.20210542"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1016\/j.cell.2015.01.049","article-title":"TREM2 lipid sensing sustains the microglial response in an Alzheimer\u2019s disease model","volume":"160","author":"Wang","year":"2015","journal-title":"Cell"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"S335","DOI":"10.3233\/JAD-221064","article-title":"Microglia-Mediated Neurovascular Unit Dysfunction in Alzheimer\u2019s Disease","volume":"94","author":"Huang","year":"2023","journal-title":"J. Alzheimers Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/0923-2494(92)80049-Q","article-title":"The role of perivascular and microglial cells in fibrillogenesis of beta-amyloid and PrP protein in Alzheimer\u2019s disease and scrapie","volume":"143","author":"Wisniewski","year":"1992","journal-title":"Res. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1007\/s004010000199","article-title":"Microglia cells are the driving force in fibrillar plaque formation, whereas astrocytes are a leading factor in plague degradation","volume":"100","author":"Wegiel","year":"2000","journal-title":"Acta Neuropathol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1056\/NEJMoa2212948","article-title":"Lecanemab in Early Alzheimer\u2019s Disease","volume":"388","author":"Swanson","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1001\/jama.2023.13239","article-title":"Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial","volume":"330","author":"Sims","year":"2023","journal-title":"JAMA"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"100052","DOI":"10.1016\/j.pharmr.2025.100052","article-title":"The microcirculation, the blood-brain barrier, and the neurovascular unit in health and Alzheimer disease: The aberrant pericyte is a central player","volume":"77","author":"Divecha","year":"2025","journal-title":"Pharmacol. Rev."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e095610","DOI":"10.1136\/bmjopen-2024-095610","article-title":"Global burden of Parkinson\u2019s disease from 1990 to 2021: A population-based study","volume":"15","author":"Li","year":"2025","journal-title":"BMJ Open"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1136\/jnnp.2007.131045","article-title":"Parkinson\u2019s disease: Clinical features and diagnosis","volume":"79","author":"Jankovic","year":"2008","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3077","DOI":"10.1093\/brain\/awaa238","article-title":"Brain-first versus body-first Parkinson\u2019s disease: A multimodal imaging case-control study","volume":"143","author":"Horsager","year":"2020","journal-title":"Brain"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"315","DOI":"10.2174\/1871527322666230330093829","article-title":"Blood-brain Barrier and Neurovascular Unit Dysfunction in Parkinson\u2019s Disease: From Clinical Insights to Pathogenic Mechanisms and Novel Therapeutic Approaches","volume":"23","author":"Khor","year":"2024","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1007\/s10571-026-01733-7","article-title":"Toxic Alpha-Synuclein and the Opening of the Gate: Blood-Brain Barrier Damage and Stepwise Leukocyte Infiltration","volume":"46","author":"Culmsee","year":"2026","journal-title":"Cell Mol. Neurobiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/1750-1326-7-42","article-title":"Exosomal cell-to-cell transmission of alpha synuclein oligomers","volume":"7","author":"Danzer","year":"2012","journal-title":"Mol. Neurodegener."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1038\/nri2171","article-title":"Evolving functions of endothelial cells in inflammation","volume":"7","author":"Pober","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.expneurol.2016.09.003","article-title":"\u03b1-Synuclein pre-formed fibrils impair tight junction protein expression without affecting cerebral endothelial cell function","volume":"285","author":"Kuan","year":"2016","journal-title":"Exp. Neurol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1756286419838354","DOI":"10.1177\/1756286419838354","article-title":"Cerebral blood flow and cerebrovascular reactivity correlate with severity of motor symptoms in Parkinson\u2019s disease","volume":"12","author":"Pelizzari","year":"2019","journal-title":"Ther. Adv. Neurol. Disord."},{"key":"ref_63","first-page":"821","article-title":"String Vessel Formation is Increased in the Brain of Parkinson Disease","volume":"5","author":"Yang","year":"2015","journal-title":"J. Park. Dis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1038\/s41598-020-80889-8","article-title":"Human \u03b1-synuclein overexpression in a mouse model of Parkinson\u2019s disease leads to vascular pathology, blood brain barrier leakage and pericyte activation","volume":"11","author":"Elabi","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s00702-011-0684-8","article-title":"Evidence for angiogenesis in Parkinson\u2019s disease, incidental Lewy body disease, and progressive supranuclear palsy","volume":"119","author":"Patel","year":"2012","journal-title":"J. Neural Transm."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1111\/j.1460-9568.2005.04281.x","article-title":"6-Hydroxydopamine-induced alterations in blood-brain barrier permeability","volume":"22","author":"Carvey","year":"2005","journal-title":"Eur. J. Neurosci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.nbd.2013.04.017","article-title":"A novel \u03b1-synuclein-GFP mouse model displays progressive motor impairment, olfactory dysfunction and accumulation of \u03b1-synuclein-GFP","volume":"56","author":"Hansen","year":"2013","journal-title":"Neurobiol. Dis."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Fo\u0142ta, J., Rzepka, Z., and Wrze\u015bniok, D. (2025). The Role of Inflammation in Neurodegenerative Diseases: Parkinson\u2019s Disease, Alzheimer\u2019s Disease, and Multiple Sclerosis. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26115177"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1007\/s00702-010-0428-1","article-title":"Neuroinflammation is a key player in Parkinson\u2019s disease and a prime target for therapy","volume":"117","author":"Qian","year":"2010","journal-title":"J. Neural Transm."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1212\/WNL.38.8.1285","article-title":"Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson\u2019s and Alzheimer\u2019s disease brains","volume":"38","author":"McGeer","year":"1988","journal-title":"Neurology"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1002\/mds.21751","article-title":"Glial reactions in Parkinson\u2019s disease","volume":"23","author":"McGeer","year":"2008","journal-title":"Mov. Disord."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1096\/fj.04-2751com","article-title":"Aggregated alpha-synuclein activates microglia: A process leading to disease progression in Parkinson\u2019s disease","volume":"19","author":"Zhang","year":"2005","journal-title":"FASEB J."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"5816","DOI":"10.1038\/s41467-019-13812-z","article-title":"Dual microglia effects on blood brain barrier permeability induced by systemic inflammation","volume":"10","author":"Haruwaka","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e15672026468149","DOI":"10.2174\/0115672026468149260326045511","article-title":"Pathophysiological Role of the Gut Brain Axis in Parkinson\u2019s Disease: From Microbial Metabolites and Intestinal Permeability to Central Neuroinflammation","volume":"23","author":"Saini","year":"2026","journal-title":"Curr. Neurovasc. Res."},{"key":"ref_75","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_76","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.neuron.2018.08.030","article-title":"PDGFR\u03b2 Cells Rapidly Relay Inflammatory Signal from the Circulatory System to Neurons via Chemokine CCL2","volume":"100","author":"Duan","year":"2018","journal-title":"Neuron"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1007\/s00401-014-1295-x","article-title":"Brain pericytes acquire a microglial phenotype after stroke","volume":"128","author":"Deierborg","year":"2014","journal-title":"Acta Neuropathol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/s10571-011-9747-5","article-title":"The possible roles of brain pericytes in brain ischemia and stroke","volume":"32","author":"Kamouchi","year":"2012","journal-title":"Cell Mol. Neurobiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.mvr.2019.03.005","article-title":"Monomeric \u03b1-synuclein induces blood-brain barrier dysfunction through activated brain pericytes releasing inflammatory mediators in vitro","volume":"124","author":"Dohgu","year":"2019","journal-title":"Microvasc. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1001\/jama.2014.3654","article-title":"Pharmacological treatment of Parkinson disease: A review","volume":"311","author":"Connolly","year":"2014","journal-title":"JAMA"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.ibneur.2023.12.007","article-title":"Pericyte derivation and transplantation for blood-CNS barrier reconstitution in CNS disorders","volume":"16","author":"Kim","year":"2024","journal-title":"IBRO Neurosci. Rep."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"5196","DOI":"10.1038\/s41467-020-19042-y","article-title":"Transplantation of hPSC-derived pericyte-like cells promotes functional recovery in ischemic stroke mice","volume":"11","author":"Sun","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Kim, H., Shin, J.Y., Lee, Y.S., Yun, S.P., Maeng, H.J., and Lee, Y. (2020). Brain Endothelial P-Glycoprotein Level Is Reduced in Parkinson\u2019s Disease via a Vitamin D Receptor-Dependent Pathway. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228538"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1970","DOI":"10.1001\/jama.2026.6385","article-title":"Amyotrophic Lateral Sclerosis: A Review","volume":"335","author":"Ravits","year":"2026","journal-title":"JAMA"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s00401-012-1039-8","article-title":"Blood-spinal cord barrier breakdown and pericyte reductions in amyotrophic lateral sclerosis","volume":"125","author":"Winkler","year":"2013","journal-title":"Acta Neuropathol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1212\/WNL.0b013e3181a41228","article-title":"Decreased mRNA expression of tight junction proteins in lumbar spinal cords of patients with ALS","volume":"72","author":"Henkel","year":"2009","journal-title":"Neurology"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1002\/jnr.22594","article-title":"Disruption of neurovascular unit prior to motor neuron degeneration in amyotrophic lateral sclerosis","volume":"89","author":"Miyazaki","year":"2011","journal-title":"J. Neurosci. Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"E1035","DOI":"10.1073\/pnas.1401595111","article-title":"Blood-spinal cord barrier disruption contributes to early motor-neuron degeneration in ALS-model mice","volume":"111","author":"Winkler","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Garbuzova-Davis, S., Saporta, S., Haller, E., Kolomey, I., Bennett, S.P., Potter, H., and Sanberg, P.R. (2007). Evidence of compromised blood-spinal cord barrier in early and late symptomatic SOD1 mice modeling ALS. PLoS ONE, 2.","DOI":"10.1371\/journal.pone.0001205"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1126\/science.1134108","article-title":"Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis","volume":"314","author":"Neumann","year":"2006","journal-title":"Science"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1002\/mus.21665","article-title":"Fus gene mutations in familial and sporadic amyotrophic lateral sclerosis","volume":"42","author":"Rademakers","year":"2010","journal-title":"Muscle Nerve"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s13041-017-0300-4","article-title":"Amyotrophic lateral sclerosis patient iPSC-derived astrocytes impair autophagy via non-cell autonomous mechanisms","volume":"10","author":"Madill","year":"2017","journal-title":"Mol. Brain"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s40035-022-00332-y","article-title":"Remodeling of astrocyte secretome in amyotrophic lateral sclerosis: Uncovering novel targets to combat astrocyte-mediated toxicity","volume":"11","author":"Ng","year":"2022","journal-title":"Transl. Neurodegener."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/978-3-319-55769-4_6","article-title":"EAAT2 and the Molecular Signature of Amyotrophic Lateral Sclerosis","volume":"16","author":"Rosenblum","year":"2017","journal-title":"Adv. Neurobiol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"297","DOI":"10.2174\/187152710791292576","article-title":"Amyotrophic lateral sclerosis and excitotoxicity: From pathological mechanism to therapeutic target","volume":"9","author":"Bogaert","year":"2010","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"3526","DOI":"10.1093\/brain\/awaa309","article-title":"The microglial component of amyotrophic lateral sclerosis","volume":"143","author":"Clarke","year":"2020","journal-title":"Brain"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"16021","DOI":"10.1073\/pnas.0607423103","article-title":"Wild-type microglia extend survival in PU.1 knockout mice with familial amyotrophic lateral sclerosis","volume":"103","author":"Beers","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Tzeplaeff, L., Wilfling, S., Requardt, M.V., and Herdick, M. (2023). Current State and Future Directions in the Therapy of ALS. Cells, 12.","DOI":"10.3390\/cells12111523"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"6857","DOI":"10.1523\/JNEUROSCI.3965-12.2013","article-title":"MicroRNAs regulate human brain endothelial cell-barrier function in inflammation: Implications for multiple sclerosis","volume":"33","author":"Reijerkerk","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_100","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_101","doi-asserted-by":"crossref","first-page":"104963","DOI":"10.1016\/j.nbd.2020.104963","article-title":"The contribution of glial cells to Huntington\u2019s disease pathogenesis","volume":"143","author":"Wilton","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1093\/hmg\/ddr475","article-title":"Mutant huntingtin\u2019s interaction with mitochondrial protein Drp1 impairs mitochondrial biogenesis and causes defective axonal transport and synaptic degeneration in Huntington\u2019s disease","volume":"21","author":"Shirendeb","year":"2012","journal-title":"Hum. Mol. Genet"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"106672","DOI":"10.1016\/j.nbd.2024.106672","article-title":"Metabolic dysregulation in Huntington\u2019s disease: Neuronal and glial perspectives","volume":"201","author":"Chang","year":"2024","journal-title":"Neurobiol. Dis."},{"key":"ref_104","first-page":"1591","article-title":"Metabolic network abnormalities in early Huntington\u2019s disease: An [(18)F]FDG PET study","volume":"42","author":"Feigin","year":"2001","journal-title":"J. Nucl. Med."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1172\/JCI45691","article-title":"Energy deficit in Huntington disease: Why it matters","volume":"121","author":"Mochel","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2893","DOI":"10.1093\/hmg\/ddy202","article-title":"TSPO-PET imaging using [18F]PBR06 is a potential translatable biomarker for treatment response in Huntington\u2019s disease: Preclinical evidence with the p75NTR ligand LM11A-31","volume":"27","author":"Simmons","year":"2018","journal-title":"Hum. Mol. Genet"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/s41582-019-0244-7","article-title":"Ageing as a risk factor for neurodegenerative disease","volume":"15","author":"Hou","year":"2019","journal-title":"Nat. Rev. Neurol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.neuron.2024.12.014","article-title":"The pathobiology of neurovascular aging","volume":"113","author":"Santisteban","year":"2025","journal-title":"Neuron"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1161\/CIRCRESAHA.118.311378","article-title":"Mechanisms of Vascular Aging","volume":"123","author":"Ungvari","year":"2018","journal-title":"Circ. Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/S0301-0082(00)00068-X","article-title":"Cerebral microvascular pathology in aging and Alzheimer\u2019s disease","volume":"64","author":"Farkas","year":"2001","journal-title":"Prog. Neurobiol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1093\/cvr\/cvy113","article-title":"Understanding the role of the perivascular space in cerebral small vessel disease","volume":"114","author":"Brown","year":"2018","journal-title":"Cardiovasc. Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"S74","DOI":"10.1111\/j.1753-4887.2010.00352.x","article-title":"Vascular basis for brain degeneration: Faltering controls and risk factors for dementia","volume":"68","author":"Kalaria","year":"2010","journal-title":"Nutr. Rev."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Hussain, B., Fang, C., and Chang, J. (2021). Blood-Brain Barrier Breakdown: An Emerging Biomarker of Cognitive Impairment in Normal Aging and Dementia. Front. Neurosci., 15.","DOI":"10.3389\/fnins.2021.688090"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Behl, T., Jayabalan, K., Ballal, S., Sahoo, S., Jayasingh Chellammal, H.S., Gulati, M., Anand, K., Jha, S.K., and Gasmi, A. (2026). A Age Related Vascular Senescence: Mystery of Blood-brain Barrier Dysfunction in Neurodegeneration. Mol. Neurobiol., 63.","DOI":"10.1007\/s12035-026-05984-9"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1177\/0271678X251320455","article-title":"Aging alters calcium signaling in vascular mural cells and drives remodeling of neurovascular coupling in the awake brain","volume":"45","author":"Zhang","year":"2025","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Jing, Y., Wang, Q., Bai, F., Li, Z., Li, Y., Liu, W., Yan, Y., Zhang, S., Gao, C., and Yu, Y. (2024). Role of microbiota-gut-brain axis in natural aging-related alterations in behavior. Front. Neurosci., 18.","DOI":"10.3389\/fnins.2024.1362239"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1111\/j.1365-2990.2012.01306.x","article-title":"Review: Microglia of the aged brain: Primed to be activated and resistant to regulation","volume":"39","author":"Norden","year":"2013","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"147ra111","DOI":"10.1126\/scitranslmed.3003748","article-title":"A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid \u03b2","volume":"4","author":"Iliff","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1002\/ana.24271","article-title":"Impairment of paravascular clearance pathways in the aging brain","volume":"76","author":"Kress","year":"2014","journal-title":"Ann. Neurol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev.publhealth.26.021304.144505","article-title":"A life course approach to chronic disease epidemiology","volume":"26","author":"Lynch","year":"2005","journal-title":"Annu Rev. Public Health"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"22480","DOI":"10.1073\/pnas.0911503106","article-title":"Expression of mutant huntingtin in mouse brain astrocytes causes age-dependent neurological symptoms","volume":"106","author":"Bradford","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s10571-025-01551-3","article-title":"Extracellular Vesicle-Derived miRNAs in Ischemic Stroke: Roles in Neuroprotection, Tissue Regeneration, and Biomarker Potential","volume":"45","author":"Eyileten","year":"2025","journal-title":"Cell Mol. Neurobiol."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Sharma, K., Zhang, Y., Paudel, K.R., Kachelmeier, A., Hansbro, P.M., and Shi, X. (2022). The Emerging Role of Pericyte-Derived Extracellular Vesicles in Vascular and Neurological Health. Cells, 11.","DOI":"10.3390\/cells11193108"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s12987-022-00317-z","article-title":"Non-coding RNAs in the regulation of blood-brain barrier functions in central nervous system disorders","volume":"19","author":"Sun","year":"2022","journal-title":"Fluids Barriers CNS"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Harati, R., Hammad, S., Tlili, A., Mahfood, M., Mabondzo, A., and Hamoudi, R. (2022). miR-27a-3p regulates expression of intercellular junctions at the brain endothelium and controls the endothelial barrier permeability. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0262152"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1007\/s13770-024-00650-4","article-title":"Extracellular Vesicles from Adipose Tissue-Derived Stromal Cells Stimulate Angiogenesis in a Scaffold-Dependent Fashion","volume":"21","author":"Getova","year":"2024","journal-title":"Tissue Eng. Regen. Med."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Sun, R., Liao, W., Lang, T., Qin, K., Jiao, K., Shao, L., Deng, C., and She, Y. (2024). Astrocyte-derived exosomal miR-378a-5p mitigates cerebral ischemic neuroinflammation by modulating NLRP3-mediated pyroptosis. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1454116"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1007\/s12311-023-01577-7","article-title":"Consensus Paper: Cerebellum and Ageing","volume":"23","author":"Arleo","year":"2024","journal-title":"Cerebellum"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.14336\/AD.2018.1105","article-title":"The Potential Markers of Circulating microRNAs and long non-coding RNAs in Alzheimer\u2019s Disease","volume":"10","author":"Zhao","year":"2019","journal-title":"Aging Dis."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"7355","DOI":"10.1007\/s00018-021-03979-4","article-title":"MicroRNA-34a: The bad guy in age-related vascular diseases","volume":"78","author":"Raucci","year":"2021","journal-title":"Cell Mol. Life Sci."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"e71466","DOI":"10.1002\/brb3.71466","article-title":"MicroRNA-Mediated Regulation of Brain Aging Hallmarks: Implications for Neurodegeneration and Neural Recovery","volume":"16","author":"Ardah","year":"2026","journal-title":"Brain Behav."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1159\/000490297","article-title":"Human Milk MicroRNAs\/Exosomes: Composition and Biological Effects","volume":"90","year":"2019","journal-title":"Nestle Nutr. Inst. Workshop Ser."},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Zhao, Y., Jaber, V., Alexandrov, P.N., Vergallo, A., Lista, S., Hampel, H., and Lukiw, W.J. (2020). microRNA-Based Biomarkers in Alzheimer\u2019s Disease (AD). Front. Neurosci., 14.","DOI":"10.3389\/fnins.2020.585432"},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Liang, Y., and Wang, L. (2021). Inflamma-MicroRNAs in Alzheimer\u2019s Disease: From Disease Pathogenesis to Therapeutic Potentials. Front Cell Neurosci., 15.","DOI":"10.3389\/fncel.2021.785433"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"5184","DOI":"10.1074\/jbc.M113.518241","article-title":"MicroRNA-339-5p down-regulates protein expression of \u03b2-site amyloid precursor protein-cleaving enzyme 1 (BACE1) in human primary brain cultures and is reduced in brain tissue specimens of Alzheimer disease subjects","volume":"289","author":"Long","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"24314","DOI":"10.18632\/oncotarget.15149","article-title":"MiR-124-3p attenuates hyperphosphorylation of Tau protein-induced apoptosis via caveolin-1-PI3K\/Akt\/GSK3\u03b2 pathway in N2a\/APP695swe cells","volume":"8","author":"Kang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"102439","DOI":"10.1016\/j.omtn.2024.102439","article-title":"Therapeutic potential and microRNA regulating properties of phytochemicals in Alzheimer\u2019s disease","volume":"36","author":"Kumari","year":"2025","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Goh, S.Y., Chao, Y.X., Dheen, S.T., Tan, E.K., and Tay, S.S. (2019). Role of MicroRNAs in Parkinson\u2019s Disease. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20225649"},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Giuliani, A., Gaetani, S., Sorgentoni, G., Agarbati, S., Laggetta, M., Matacchione, G., Gobbi, M., Rossi, T., Galeazzi, R., and Piccinini, G. (2021). Circulating Inflamma-miRs as Potential Biomarkers of Cognitive Impairment in Patients Affected by Alzheimer\u2019s Disease. Front. Aging Neurosci., 13.","DOI":"10.3389\/fnagi.2021.647015"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1523\/ENEURO.0393-21.2021","article-title":"Mechanism of miR-132-3p Promoting Neuroinflammation and Dopaminergic Neurodegeneration in Parkinson\u2019s Disease","volume":"9","author":"Gong","year":"2022","journal-title":"eNeuro"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"104515","DOI":"10.1016\/j.phrs.2019.104515","article-title":"miR-124 and Parkinson\u2019s disease: A biomarker with therapeutic potential","volume":"150","author":"Angelopoulou","year":"2019","journal-title":"Pharmacol. Res."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/j.biopsych.2018.12.008","article-title":"MicroRNA-26a\/Death-Associated Protein Kinase 1 Signaling Induces Synucleinopathy and Dopaminergic Neuron Degeneration in Parkinson\u2019s Disease","volume":"85","author":"Su","year":"2019","journal-title":"Biol. Psychiatry"},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"\u00dcnal, Y., Akba\u015f, D., \u00d6zdemir, \u00c7., and Edg\u00fcnl\u00fc, T. (2026). Dysregulated MicroRNAs in Parkinson\u2019s Disease: Pathogenic Mechanisms and Biomarker Potential. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27020930"},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Bougea, A. (2026). Targeting Non-Coding RNAs as a Potential Therapeutic and Delivery Strategy Against Neurodegenerative Diseases. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27073260"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"7027380","DOI":"10.1155\/2017\/7027380","article-title":"Potential Roles of Exosomal MicroRNAs as Diagnostic Biomarkers and Therapeutic Application in Alzheimer\u2019s Disease","volume":"2017","author":"Chen","year":"2017","journal-title":"Neural Plast."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/978-1-4614-3209-8_33","article-title":"Oxidized low-density-lipoprotein-induced injury in retinal pigment epithelium alters expression of the membrane complement regulatory factors CD46 and CD59 through exosomal and apoptotic bleb release","volume":"801","author":"Ebrahimi","year":"2014","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_147","first-page":"292","article-title":"Theranostics and contrast-agents for medical imaging: A pharmaceutical company viewpoint","volume":"3","author":"Louguet","year":"2013","journal-title":"Quant. Imaging Med. Surg."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"305","DOI":"10.2174\/1872210517666230403105152","article-title":"Nanoneuroscience: Cutting-edge Approach for Disease Management","volume":"18","author":"Malhotra","year":"2024","journal-title":"Recent Pat. Nanotechnol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1021\/acs.bioconjchem.4c00293","article-title":"Lipid Nanoparticles for Brain Tumor Theranostics: Challenges and Status","volume":"35","author":"Kaur","year":"2024","journal-title":"Bioconjug Chem."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"100342","DOI":"10.1016\/j.celbio.2025.100342","article-title":"mRNA-based MRI contrast agent for precise diagnosis of glioma and pseudoprogression","volume":"2","author":"Li","year":"2026","journal-title":"Cell Biomater."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Hasanpour-Segherlou, Z., Alikhani, A., Bertola, L., Rupp, C., Haghighi, M., Kim, J., Rawson, C., Baloi, A., Hosseini, F., and Pahlevani, M. (2026). Integrating Endovascular Drug Delivery into the Therapeutic Landscape of Glioblastoma. Cancers, 18.","DOI":"10.3390\/cancers18142278"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"e13895575451920","DOI":"10.2174\/0113895575451920260708183100","article-title":"Aptamer-carbon Nanotube Hybrids: Emerging Frontiers in Biomedical Diagnostics and Therapeutics","volume":"26","author":"Bhosale","year":"2026","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Huemer, F., Leisch, M., Geisberger, R., Zaborsky, N., and Greil, R. (2021). MiRNA-Based Therapeutics in the Era of Immune-Checkpoint Inhibitors. Pharmaceuticals, 14.","DOI":"10.3390\/ph14020089"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"111800","DOI":"10.1016\/j.mad.2023.111800","article-title":"Integration of miRNA\u2019s theranostic potential with nanotechnology: Promises and challenges for Parkinson\u2019s disease therapeutics","volume":"211","author":"Jain","year":"2023","journal-title":"Mech. Ageing Dev."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"2210","DOI":"10.1007\/s12247-023-09785-8","article-title":"Development, Optimization, and Evaluation of Nano-platforms for Delivery of siRNA and BPTES in c-Myc Induced Breast Cancer","volume":"18","author":"Paul","year":"2023","journal-title":"J. Pharm. Innov."},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Ngowi, E.E., Wang, Y.Z., Qian, L., Helmy, Y.A.S.H., Anyomi, B., Li, T., Zheng, M., Jiang, E.S., Duan, S.F., and Wei, J.S. (2021). The Application of Nanotechnology for the Diagnosis and Treatment of Brain Diseases and Disorders. Front. Bioeng. Biotechnol., 9.","DOI":"10.3389\/fbioe.2021.629832"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"2050032","DOI":"10.1142\/S012906572050032X","article-title":"Automated MRI-Based Deep Learning Model for Detection of Alzheimer\u2019s Disease Process","volume":"30","author":"Feng","year":"2020","journal-title":"Int. J. Neural Syst."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/j.ymthe.2018.03.008","article-title":"Targeting Biological Barriers: Turning a Wall into a Therapeutic Springboard","volume":"26","author":"Moghimi","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"129510","DOI":"10.1016\/j.talanta.2026.129510","article-title":"Recent advances on miRNAs in extracellular vesicles: Molecular mechanisms, detection methods, and clinical applications","volume":"303","author":"Zhao","year":"2026","journal-title":"Talanta"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1111\/j.2042-7158.1973.tb10010.x","article-title":"Use of substituent constants in structure-activity relations and the importance of the choice of standard state","volume":"25","author":"Davis","year":"1973","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"609510","DOI":"10.2147\/IJN.S609510","article-title":"MRI-Guided Magnetic Micro\/Nanorobots for Precision Neurotherapeutics: From Intelligent Navigation and BBB Penetration to Clinical Translation","volume":"21","author":"Xu","year":"2026","journal-title":"Int. J. Nanomed."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"5631","DOI":"10.1038\/s41467-019-13576-6","article-title":"Active generation and magnetic actuation of microrobotic swarms in bio-fluids","volume":"10","author":"Yu","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"Ji, F., Li, T., Villa, K., and Dong, Y. (2024). Editorial: Micro\/nanorobots in nanobiotechnology. Front Bioeng. Biotechnol., 12.","DOI":"10.3389\/fbioe.2024.1453307"},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Arco, J.E., Alizadehsani, R., Atzmueller, M., Barakova, E., Bloch, L., Bologna, G., Bonomini, P., Cho, S.B., Cortes, J.M., and Elazab, A. (2026). Advancing multimodal neuroimaging: Explainable and responsible AI for early dementia detection. Neuroimage, 122142.","DOI":"10.1016\/j.neuroimage.2026.122142"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"82S","DOI":"10.2967\/jnmt.125.270251","article-title":"The Role of Artificial Intelligence in Theranostics","volume":"53","author":"Currie","year":"2025","journal-title":"J. Nucl. Med. Technol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"2186","DOI":"10.1038\/s41598-026-35404-w","article-title":"Artificial intelligence and precision medicine","volume":"16","author":"Ahmed","year":"2026","journal-title":"Sci. Rep."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"110695","DOI":"10.1016\/j.jneumeth.2026.110695","article-title":"Artificial intelligence and machine learning driven nanorobotics for targeted brain delivery: Redefining blood-brain barrier navigation","volume":"429","author":"Kumar","year":"2026","journal-title":"J. Neurosci. Methods"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1038\/s41392-026-02631-6","article-title":"Multi-omics and artificial intelligence for precision drug discovery and potential clinical applications","volume":"11","author":"Liu","year":"2026","journal-title":"Signal Transduct. Target Ther."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"3249","DOI":"10.1021\/acsbiomaterials.6c00187","article-title":"AI-Driven Design and Clinical Translation of Nucleotide-Peptide and Peptide-Drug Conjugates","volume":"12","author":"Pandey","year":"2026","journal-title":"ACS Biomater. Sci. Eng."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7165\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T08:13:57Z","timestamp":1786436037000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7165"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,11]]},"references-count":169,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27167165"],"URL":"https:\/\/doi.org\/10.3390\/ijms27167165","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,11]]}}}