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Unfortunately, no cure exists for these disorders, but the actual therapies are only able to ameliorate people\u2019s quality of life. Thus, there is an urgent need to test potential therapeutic approaches. Brain organoids are a possible valuable tool in the study of the brain, due to their ability to reproduce different brain regions and maturation stages; they can be used also as a tool for disease modelling and target identification of neurological disorders. Recently, brain organoids have been used in drug-screening processes, even if there are several limitations to overcome. This review focuses on the description of brain organoid development and drug-screening processes, discussing the advantages, challenges, and limitations of the use of organoids in modeling neurological diseases. We also highlighted the potential of testing novel therapeutic approaches. Finally, we examine the challenges and future directions to improve the drug-screening process.<\/jats:p>","DOI":"10.3390\/pharmaceutics16040443","type":"journal-article","created":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T12:50:49Z","timestamp":1711371049000},"page":"443","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Brain Organoids: A Game-Changer for Drug Testing"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4210-9141","authenticated-orcid":false,"given":"Chiara","family":"Giorgi","sequence":"first","affiliation":[{"name":"Department of Life, Health and Environmental Science, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0548-605X","authenticated-orcid":false,"given":"Giorgia","family":"Lombardozzi","sequence":"additional","affiliation":[{"name":"Department of Life, Health and Environmental Science, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Ammannito","sequence":"additional","affiliation":[{"name":"Department of Life, Health and Environmental Science, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0959-7300","authenticated-orcid":false,"given":"Marta Sofia","family":"Scenna","sequence":"additional","affiliation":[{"name":"Department of Life, Health and Environmental Science, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9929-6376","authenticated-orcid":false,"given":"Eleonora","family":"Maceroni","sequence":"additional","affiliation":[{"name":"Department of Life, Health and Environmental Science, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimiliano","family":"Quintiliani","sequence":"additional","affiliation":[{"name":"Department of Life, Health and Environmental Science, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3693-840X","authenticated-orcid":false,"given":"Michele","family":"d\u2019Angelo","sequence":"additional","affiliation":[{"name":"Department of Life, Health and Environmental Science, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2737-7970","authenticated-orcid":false,"given":"Annamaria","family":"Cimini","sequence":"additional","affiliation":[{"name":"Department of Life, Health and Environmental Science, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7005-3218","authenticated-orcid":false,"given":"Vanessa","family":"Castelli","sequence":"additional","affiliation":[{"name":"Department of Life, Health and Environmental Science, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Lima, A.A., Mridha, M.F., Das, S.C., Kabir, M.M., Islam, M.R., and Watanobe, Y. (2022). A Comprehensive Survey on the Detection, Classification, and Challenges of Neurological Disorders. Biology, 11.","DOI":"10.3390\/biology11030469"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"04160","DOI":"10.7189\/jogh.13.04160","article-title":"Global, Regional, and National Burden of Neurological Disorders in 204 Countries and Territories Worldwide","volume":"13","author":"Huang","year":"2023","journal-title":"J. Glob. Health"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/S1474-4422(18)30499-X","article-title":"Global, Regional, and National Burden of Neurological Disorders, 1990\u20132016: A Systematic Analysis for the Global Burden of Disease Study 2016","volume":"18","author":"Feigin","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1159\/000504292","article-title":"Artificial Intelligence Techniques for Automated Diagnosis of Neurological Disorders","volume":"82","author":"Raghavendra","year":"2019","journal-title":"Eur. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.neurol.2020.01.356","article-title":"Epidemiology of Neurological Diseases in Older Adults","volume":"176","author":"Dumurgier","year":"2020","journal-title":"Rev. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e105","DOI":"10.1016\/S2468-2667(21)00249-8","article-title":"Estimation of the Global Prevalence of Dementia in 2019 and Forecasted Prevalence in 2050: An Analysis for the Global Burden of Disease Study 2019","volume":"7","author":"Nichols","year":"2022","journal-title":"Lancet Public Health"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"833","DOI":"10.3233\/JAD-190924","article-title":"Alzheimer\u2019s Disease or Behavioral Variant Frontotemporal Dementia? Review of Key Points Toward an Accurate Clinical and Neuropsychological Diagnosis","volume":"73","author":"Musa","year":"2020","journal-title":"J. Alzheimers Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S75","DOI":"10.1016\/j.ypmed.2011.01.023","article-title":"The Combined Effects of Exercise and Foods in Preventing Neurological and Cognitive Disorders","volume":"52","year":"2011","journal-title":"Prev. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"70","DOI":"10.7196\/SAMJ.2019.v109i8b.14009","article-title":"Stem Cell Therapy for Neurological Disorders","volume":"109","author":"Alessandrini","year":"2019","journal-title":"S. Afr. Med. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1080\/1061186X.2019.1630415","article-title":"Gene Therapy for Neurological Disorders: Challenges and Recent Advancements","volume":"28","author":"Pena","year":"2020","journal-title":"J. Drug Target."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Costamagna, G., Comi, G.P., and Corti, S. (2021). Advancing Drug Discovery for Neurological Disorders Using iPSC-Derived Neural Organoids. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052659"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1056\/NEJMra1806175","article-title":"Organoids\u2014Preclinical Models of Human Disease","volume":"380","author":"Li","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/s41401-022-00986-4","article-title":"Humanized Cerebral Organoids-Based Ischemic Stroke Model for Discovering of Potential Anti-Stroke Agents","volume":"44","author":"Wang","year":"2023","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_14","first-page":"1884","article-title":"Brain Organoids Are New Tool for Drug Screening of Neurological Diseases","volume":"18","author":"Zhou","year":"2023","journal-title":"Neural Regen. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1038\/nprot.2014.158","article-title":"Generation of Cerebral Organoids from Human Pluripotent Stem Cells","volume":"9","author":"Lancaster","year":"2014","journal-title":"Nat. Protoc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1038\/s41593-020-00730-3","article-title":"Brain Organoids for the Study of Human Neurobiology at the Interface of in Vitro and in Vivo","volume":"23","author":"Chiaradia","year":"2020","journal-title":"Nat. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1126\/science.25.649.912","article-title":"A New Method by Which Sponges May Be Artificially Reared","volume":"25","author":"Wilson","year":"1907","journal-title":"Science"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"C151","DOI":"10.1152\/ajpcell.00120.2020","article-title":"A Brief History of Organoids","volume":"319","author":"Novellasdemunt","year":"2020","journal-title":"Am. J. Physiol.-Cell Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1111\/brv.12626","article-title":"Modelling Neurodegenerative Diseases with 3D Brain Organoids","volume":"95","author":"Chang","year":"2020","journal-title":"Biol. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7634","DOI":"10.1073\/pnas.78.12.7634","article-title":"Isolation of a Pluripotent Cell Line from Early Mouse Embryos Cultured in Medium Conditioned by Teratocarcinoma Stem Cells","volume":"78","author":"Martin","year":"1981","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1126\/science.282.5391.1145","article-title":"Embryonic Stem Cell Lines Derived from Human Blastocysts","volume":"282","author":"Thomson","year":"1998","journal-title":"Science"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.stem.2008.09.002","article-title":"Self-Organized Formation of Polarized Cortical Tissues from ESCs and Its Active Manipulation by Extrinsic Signals","volume":"3","author":"Eiraku","year":"2008","journal-title":"Cell Stem Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1038\/nature07935","article-title":"Single Lgr5 Stem Cells Build Crypt-Villus Structures in Vitro without a Mesenchymal Niche","volume":"459","author":"Sato","year":"2009","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.stem.2013.04.009","article-title":"Next-Generation Regenerative Medicine: Organogenesis from Stem Cells in 3D Culture","volume":"12","author":"Sasai","year":"2013","journal-title":"Cell Stem Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1038\/nature11859","article-title":"Cytosystems Dynamics in Self-Organization of Tissue Architecture","volume":"493","author":"Sasai","year":"2013","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1007\/s12015-021-10147-5","article-title":"Culture Variabilities of Human iPSC-Derived Cerebral Organoids Are a Major Issue for the Modelling of Phenotypes Observed in Alzheimer\u2019s Disease","volume":"18","author":"Rooney","year":"2022","journal-title":"Stem Cell Rev. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s13229-017-0124-1","article-title":"CRISPR\/Cas9-Mediated Heterozygous Knockout of the Autism Gene CHD8 and Characterization of Its Transcriptional Networks in Cerebral Organoids Derived from iPS Cells","volume":"8","author":"Wang","year":"2017","journal-title":"Mol. Autism"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.neuint.2016.10.004","article-title":"Neural Organoids for Disease Phenotyping, Drug Screening and Developmental Biology Studies","volume":"106","author":"Hartley","year":"2017","journal-title":"Neurochem. Int."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1016\/j.cell.2016.04.032","article-title":"Brain-Region-Specific Organoids Using Mini-Bioreactors for Modeling ZIKV Exposure","volume":"165","author":"Qian","year":"2016","journal-title":"Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/978-1-59745-443-8_8","article-title":"Generation of Multicellular Tumor Spheroids by the Hanging-Drop Method","volume":"Volume 140","author":"Hauser","year":"2007","journal-title":"Tissue Engineering"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Zhang, Z., O\u2019Laughlin, R., Song, H., and Ming, G. (2022). Patterning of Brain Organoids Derived from Human Pluripotent Stem Cells. Curr. Opin. Neurobiol., 74.","DOI":"10.1016\/j.conb.2022.102536"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.stem.2017.07.007","article-title":"Fusion of Regionally Specified hPSC-Derived Organoids Models Human Brain Development and Interneuron Migration","volume":"21","author":"Xiang","year":"2017","journal-title":"Cell Stem Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1038\/nmeth.4304","article-title":"Fused Cerebral Organoids Model Interactions between Brain Regions","volume":"14","author":"Bagley","year":"2017","journal-title":"Nat. Methods"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"20284","DOI":"10.1073\/pnas.1315710110","article-title":"Self-Organization of Axial Polarity, inside-out Layer Pattern, and Species-Specific Progenitor Dynamics in Human ES Cell\u2013Derived Neocortex","volume":"110","author":"Kadoshima","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/nature22047","article-title":"Cell Diversity and Network Dynamics in Photosensitive Human Brain Organoids","volume":"545","author":"Quadrato","year":"2017","journal-title":"Nature"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.neuron.2015.12.008","article-title":"The Cellular and Molecular Landscapes of the Developing Human Central Nervous System","volume":"89","author":"Silbereis","year":"2016","journal-title":"Neuron"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"O\u2019Rahilly, R., and M\u00fcller, F. (2006). The Embryonic Human Brain: An Atlas of Developmental Stages, Wiley. [1st ed.].","DOI":"10.1002\/0471973084"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.1016\/j.celrep.2020.01.038","article-title":"Synthetic Analyses of Single-Cell Transcriptomes from Multiple Brain Organoids and Fetal Brain","volume":"30","author":"Tanaka","year":"2020","journal-title":"Cell Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"dev166074","DOI":"10.1242\/dev.166074","article-title":"Brain Organoids: Advances, Applications and Challenges","volume":"146","author":"Qian","year":"2019","journal-title":"Development"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/nature12517","article-title":"Cerebral Organoids Model Human Brain Development and Microcephaly","volume":"501","author":"Lancaster","year":"2013","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1038\/s41593-019-0350-2","article-title":"Cerebral Organoids at the Air\u2013Liquid Interface Generate Diverse Nerve Tracts with Functional Output","volume":"22","author":"Giandomenico","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/j.stem.2020.02.002","article-title":"Sliced Human Cortical Organoids for Modeling Distinct Cortical Layer Formation","volume":"26","author":"Qian","year":"2020","journal-title":"Cell Stem Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1038\/nn1402","article-title":"Directed Differentiation of Telencephalic Precursors from Embryonic Stem Cells","volume":"8","author":"Watanabe","year":"2005","journal-title":"Nat. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1038\/nbt1310","article-title":"A ROCK Inhibitor Permits Survival of Dissociated Human Embryonic Stem Cells","volume":"25","author":"Watanabe","year":"2007","journal-title":"Nat. Biotechnol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.stem.2016.07.005","article-title":"Midbrain-like Organoids from Human Pluripotent Stem Cells Contain Functional Dopaminergic and Neuromelanin-Producing Neurons","volume":"19","author":"Jo","year":"2016","journal-title":"Cell Stem Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1016\/j.stem.2021.04.006","article-title":"Generation of Hypothalamic Arcuate Organoids from Human Induced Pluripotent Stem Cells","volume":"28","author":"Huang","year":"2021","journal-title":"Cell Stem Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"eaaz5626","DOI":"10.1126\/science.aaz5626","article-title":"Human CNS Barrier-Forming Organoids with Cerebrospinal Fluid Production","volume":"369","author":"Pellegrini","year":"2020","journal-title":"Science"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.4103\/1673-5374.255966","article-title":"Spinal Cord Organoids Add an Extra Dimension to Traditional Motor Neuron Cultures","volume":"14","author":"Winanto","year":"2019","journal-title":"Neural Regen. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.neuron.2018.10.007","article-title":"Building Models of Brain Disorders with Three-Dimensional Organoids","volume":"100","author":"Amin","year":"2018","journal-title":"Neuron"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"eaay8828","DOI":"10.1126\/sciadv.aay8828","article-title":"A 3D Human Brain\u2013like Tissue Model of Herpes-Induced Alzheimer\u2019s Disease","volume":"6","author":"Cairns","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.stemcr.2019.01.020","article-title":"Modeling G2019S-LRRK2 Sporadic Parkinson\u2019s Disease in 3D Midbrain Organoids","volume":"12","author":"Kim","year":"2019","journal-title":"Stem Cell Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1016\/j.stem.2019.04.014","article-title":"OLIG2 Drives Abnormal Neurodevelopmental Phenotypes in Human iPSC-Based Organoid and Chimeric Mouse Models of Down Syndrome","volume":"24","author":"Xu","year":"2019","journal-title":"Cell Stem Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/s41422-019-0152-9","article-title":"Zika Virus Infection Induces RNAi-Mediated Antiviral Immunity in Human Neural Progenitors and Brain Organoids","volume":"29","author":"Xu","year":"2019","journal-title":"Cell Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1038\/s41592-018-0070-7","article-title":"Genetically Engineered Cerebral Organoids Model Brain Tumor Formation","volume":"15","author":"Bian","year":"2018","journal-title":"Nat. Methods"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/s41586-023-06713-1","article-title":"iPS-Cell-Derived Microglia Promote Brain Organoid Maturation via Cholesterol Transfer","volume":"623","author":"Park","year":"2023","journal-title":"Nature"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Fan, W., Christian, K.M., Song, H., and Ming, G.-L. (2022). Applications of Brain Organoids for Infectious Diseases. J. Mol. Biol., 434.","DOI":"10.1016\/j.jmb.2021.167243"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.scr.2013.02.001","article-title":"Differentiation of Serum-Free Embryoid Bodies from Human Induced Pluripotent Stem Cells into Networks","volume":"10","author":"Nestor","year":"2013","journal-title":"Stem Cell Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1038\/s41593-018-0236-8","article-title":"Animal Models of Neurodegenerative Diseases","volume":"21","author":"Dawson","year":"2018","journal-title":"Nat. Neurosci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"108627","DOI":"10.1016\/j.jneumeth.2020.108627","article-title":"High-Throughput Screening of Human Induced Pluripotent Stem Cell-Derived Brain Organoids","volume":"335","author":"Durens","year":"2020","journal-title":"J. Neurosci. Methods"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/s41392-022-01024-9","article-title":"Human Organoids in Basic Research and Clinical Applications","volume":"7","author":"Tang","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.1038\/s41380-018-0229-8","article-title":"Modeling Amyloid Beta and Tau Pathology in Human Cerebral Organoids","volume":"23","author":"Gonzalez","year":"2018","journal-title":"Mol. Psychiatry"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"57","DOI":"10.3389\/fped.2019.00057","article-title":"Modeling Human Brain Circuitry Using Pluripotent Stem Cell Platforms","volume":"7","author":"Hartlaub","year":"2019","journal-title":"Front. Pediatr."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1007\/s42242-021-00150-7","article-title":"Organoids: A Novel Modality in Disease Modeling","volume":"4","author":"Heydari","year":"2021","journal-title":"Bio-Des. Manuf."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s40164-018-0122-9","article-title":"Organoid Technology in Disease Modelling, Drug Development, Personalized Treatment and Regeneration Medicine","volume":"7","author":"Xu","year":"2018","journal-title":"Exp. Hematol. Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1186\/s13287-021-02369-8","article-title":"Brain Organoid: A 3D Technology for Investigating Cellular Composition and Interactions in Human Neurological Development and Disease Models in Vitro","volume":"12","author":"Agboola","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/j.cell.2015.03.053","article-title":"Prospective Derivation of a Living Organoid Biobank of Colorectal Cancer Patients","volume":"161","author":"Francies","year":"2015","journal-title":"Cell"},{"key":"ref_67","unstructured":"(2024, March 11). Generation of Vascularized Brain Organoids to Study Neurovascular Interactions|eLife. Available online: https:\/\/elifesciences.org\/articles\/76707."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1038\/nbt.4127","article-title":"An in Vivo Model of Functional and Vascularized Human Brain Organoids","volume":"36","author":"Mansour","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1038\/s41592-019-0586-5","article-title":"Engineering of Human Brain Organoids with a Functional Vascular-like System","volume":"16","author":"Cakir","year":"2019","journal-title":"Nat. Methods"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"12516","DOI":"10.1073\/pnas.1516645112","article-title":"Human Pluripotent Stem Cell-Derived Neural Constructs for Predicting Neural Toxicity","volume":"112","author":"Schwartz","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1038\/nbt.3906","article-title":"Guided Self-Organization and Cortical Plate Formation in Human Brain Organoids","volume":"35","author":"Lancaster","year":"2017","journal-title":"Nat. Biotechnol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3369","DOI":"10.1016\/j.celrep.2016.12.001","article-title":"Cerebral Organoids Recapitulate Epigenomic Signatures of the Human Fetal Brain","volume":"17","author":"Luo","year":"2016","journal-title":"Cell Rep."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1002\/stem.2852","article-title":"Concise Review: Current Status of Three-Dimensional Organoids as Preclinical Models","volume":"36","author":"Kaushik","year":"2018","journal-title":"Stem Cells"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1080\/14656566.2017.1359255","article-title":"Ataluren in Cystic Fibrosis: Development, Clinical Studies and Where Are We Now?","volume":"18","author":"Haq","year":"2017","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Lin, X., Li, X., and Lin, X. (2020). A Review on Applications of Computational Methods in Drug Screening and Design. Molecules, 25.","DOI":"10.3390\/molecules25061375"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.cell.2019.01.017","article-title":"Establishing Cerebral Organoids as Models of Human-Specific Brain Evolution","volume":"176","author":"Pollen","year":"2019","journal-title":"Cell"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1016\/j.neuron.2020.09.001","article-title":"Resolving Neurodevelopmental and Vision Disorders Using Organoid Single-Cell Multi-Omics","volume":"107","author":"Brancati","year":"2020","journal-title":"Neuron"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e52904","DOI":"10.7554\/eLife.52904","article-title":"A Fully Automated High-Throughput Workflow for 3D-Based Chemical Screening in Human Midbrain Organoids","volume":"9","author":"Renner","year":"2020","journal-title":"eLife"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1038\/s41467-020-20440-5","article-title":"A Logical Network-Based Drug-Screening Platform for Alzheimer\u2019s Disease Representing Pathological Features of Human Brain Organoids","volume":"12","author":"Park","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1056\/NEJMra0909142","article-title":"Alzheimer\u2019s Disease","volume":"362","author":"Querfurth","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jalz.2011.10.007","article-title":"National Institute on Aging\u2013Alzheimer\u2019s Association Guidelines for the Neuropathologic Assessment of Alzheimer\u2019s Disease","volume":"8","author":"Hyman","year":"2012","journal-title":"Alzheimers Dement."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/nrneurol.2012.263","article-title":"Apolipoprotein E and Alzheimer Disease: Risk, Mechanisms and Therapy","volume":"9","author":"Liu","year":"2013","journal-title":"Nat. Rev. Neurol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Raja, W.K., Mungenast, A.E., Lin, Y.-T., Ko, T., Abdurrob, F., Seo, J., and Tsai, L.-H. (2016). Self-Organizing 3D Human Neural Tissue Derived from Induced Pluripotent Stem Cells Recapitulate Alzheimer\u2019s Disease Phenotypes. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0161969"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Oishi, T., Koizumi, S., and Kurozumi, K. (2022). Molecular Mechanisms and Clinical Challenges of Glioma Invasion. Brain Sci., 12.","DOI":"10.3390\/brainsci12020291"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"3472","DOI":"10.1158\/0008-5472.CAN-08-3886","article-title":"Human Glioblastoma\u2013Derived Cancer Stem Cells: Establishment of Invasive Glioma Models and Treatment with Oncolytic Herpes Simplex Virus Vectors","volume":"69","author":"Wakimoto","year":"2009","journal-title":"Cancer Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/bs.ircmb.2020.08.001","article-title":"Novel Facets of Glioma Invasion","volume":"Volume 360","author":"Fabian","year":"2021","journal-title":"International Review of Cell and Molecular Biology"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.canlet.2016.01.024","article-title":"CGCG Clinical Practice Guidelines for the Management of Adult Diffuse Gliomas","volume":"375","author":"Jiang","year":"2016","journal-title":"Cancer Lett."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.canlet.2020.12.013","article-title":"A Novel Integrated System Using Patient-Derived Glioma Cerebral Organoids and Xenografts for Disease Modeling and Drug Screening","volume":"500","author":"Zhang","year":"2021","journal-title":"Cancer Lett."},{"key":"ref_89","first-page":"697","article-title":"Unraveling the Details of Prion (Con)Formation(s): Recent Advances by Mass Spectrometry","volume":"11","author":"Principe","year":"2008","journal-title":"Curr. Opin. Drug Discov. Devel."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"5165","DOI":"10.1038\/s41598-021-84689-6","article-title":"Human Cerebral Organoids as a Therapeutic Drug Screening Model for Creutzfeldt\u2013Jakob Disease","volume":"11","author":"Groveman","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/B978-0-444-63945-5.00009-X","article-title":"Sporadic Creutzfeldt\u2013Jakob Disease","volume":"Volume 153","author":"Zerr","year":"2018","journal-title":"Handbook of Clinical Neurology"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1016\/B978-0-444-52910-7.00040-4","article-title":"Creutzfeldt\u2013Jakob Disease","volume":"Volume 112","year":"2013","journal-title":"Handbook of Clinical Neurology"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1007\/s00401-012-1002-8","article-title":"Consensus Classification of Human Prion Disease Histotypes Allows Reliable Identification of Molecular Subtypes: An Inter-Rater Study among Surveillance Centres in Europe and USA","volume":"124","author":"Parchi","year":"2012","journal-title":"Acta Neuropathol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1111\/imm.12134","article-title":"Innate and Adaptive Immune Responses in Neurodegeneration and Repair","volume":"141","author":"Amor","year":"2014","journal-title":"Immunology"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s00401-010-0779-6","article-title":"Phenotypic Variability of Sporadic Human Prion Disease and Its Molecular Basis: Past, Present, and Future","volume":"121","author":"Parchi","year":"2011","journal-title":"Acta Neuropathol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"8866","DOI":"10.1523\/JNEUROSCI.19-20-08866.1999","article-title":"Hans Kretzschmar Evidence of Presynaptic Location and Function of the Prion Protein","volume":"19","author":"Herms","year":"1999","journal-title":"J. Neurosci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1128\/jvi.67.2.643-650.1993","article-title":"Sulfated Polyanion Inhibition of Scrapie-Associated PrP Accumulation in Cultured Cells","volume":"67","author":"Caughey","year":"1993","journal-title":"J. Virol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1099\/0022-1317-72-2-457","article-title":"Chemoprophylaxis of Scrapie in Mice","volume":"72","author":"Diringer","year":"1991","journal-title":"J. Gen. Virol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"4276","DOI":"10.1038\/s41467-019-12152-2","article-title":"NPC1 Regulates ER Contacts with Endocytic Organelles to Mediate Cholesterol Egress","volume":"10","author":"Burgoyne","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1038\/s41419-020-03262-7","article-title":"Human iNSC-Derived Brain Organoid Model of Lysosomal Storage Disorder in Niemann\u2013Pick Disease Type C","volume":"11","author":"Lee","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"719","DOI":"10.4161\/auto.19469","article-title":"Autophagy in Lysosomal Storage Disorders","volume":"8","author":"Lieberman","year":"2012","journal-title":"Autophagy"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s13023-018-0785-7","article-title":"Consensus Clinical Management Guidelines for Niemann-Pick Disease Type C","volume":"13","author":"Geberhiwot","year":"2018","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"767621","DOI":"10.3389\/fgene.2021.767621","article-title":"Human Organoids for Predictive Toxicology Research and Drug Development","volume":"12","author":"Matsui","year":"2021","journal-title":"Front. Genet."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s00604-023-06165-4","article-title":"Humanized Brain Organoids-on-Chip Integrated with Sensors for Screening Neuronal Activity and Neurotoxicity","volume":"191","author":"Yildirim","year":"2024","journal-title":"Microchim. Acta"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/16\/4\/443\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:18:20Z","timestamp":1760105900000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/16\/4\/443"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,22]]},"references-count":104,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["pharmaceutics16040443"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics16040443","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,22]]}}}