{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T17:38:39Z","timestamp":1794332319761,"version":"4.9.0"},"reference-count":68,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p>Neurodegenerative diseases such as Alzheimer\u2019s disease (AD), Parkinson\u2019s disease (PD), and amyotrophic lateral sclerosis (ALS) have become major global causes of disability and mortality. Their complex pathogenic mechanisms remain incompletely understood, and effective disease-modifying therapies are still lacking. Traditional animal models and two-dimensional (2D) cell culture systems exhibit notable limitations in structural complexity, human relevance, and translational validity, making it difficult to faithfully recapitulate human-specific neuropathology. In recent years, brain organoid technology derived from induced pluripotent stem cells (iPSCs) has advanced rapidly, enabling the self-organization of diverse neuronal and glial cell types within a three-dimensional (3D) architecture that partially mimics human brain development and disease-related pathological events. When integrated with CRISPR\u2013Cas9-based genome editing and multi-omics profiling, organoids support causal mechanism studies, target validation, and individualized drug-response prediction, highlighting their growing value in early-stage drug discovery. Despite current challenges\u2014including insufficient maturation, lack of vascularization and immune components, and batch variability\u2014the continuous progress in bioengineering, microfluidic systems, and artificial intelligence (AI)\u2013driven multimodal data analysis is steadily expanding the translational potential of organoids as human-relevant preclinical models. Overall, brain organoids provide an essential foundation for constructing physiologically relevant and predictive research platforms for neurodegenerative diseases, offering new opportunities for therapeutic development and precision medicine.<\/jats:p>","DOI":"10.3389\/fnins.2026.1764964","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T06:56:28Z","timestamp":1771397788000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Brain organoids as precision models for neurodegenerative diseases: from disease modeling to drug discovery"],"prefix":"10.3389","volume":"20","author":[{"given":"Yanxu","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Radiology, The Sixth Medical Center of PLA General Hospital","place":["Beijing, China"]},{"name":"Xiangya School of Medicine, Central South University","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenke","family":"Zhou","sequence":"additional","affiliation":[{"name":"Xiangya School of Medicine, Central South University","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haozhe","family":"Chang","sequence":"additional","affiliation":[{"name":"Xiangya School of Medicine, Central South University","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuihong","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Radiology, The Sixth Medical Center of PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"842","DOI":"10.3390\/cells14110842","article-title":"Brain organoids and assembloids\u2014from disease modeling to drug discovery","volume":"14","author":"Ajongbolo","year":"2025","journal-title":"Cells"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"3573","DOI":"10.1021\/acssensors.4c00476","article-title":"Drug evaluation of Parkinson's disease patient-derived midbrain organoids using mesoporous au Nanodot-patterned 3D concave electrode","volume":"9","author":"An","year":"2024","journal-title":"ACS Sens."},{"key":"ref3","doi-asserted-by":"publisher","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. 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