{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:57:20Z","timestamp":1792036640923,"version":"4.4.0"},"reference-count":158,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T00:00:00Z","timestamp":1736726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In vitro models play a pivotal role in advancing our understanding of neurodegenerative diseases (NDs) such as Parkinson\u2019s and Alzheimer\u2019s disease (PD and AD). Traditionally, 2D cell cultures have been instrumental in elucidating the cellular mechanisms underlying these diseases. Cultured cells derived from patients or animal models provide valuable insights into the pathological processes at the cellular level. However, they often lack the native tissue environment complexity, limiting their ability to fully recapitulate their features. In contrast, 3D models offer a more physiologically relevant platform by mimicking the 3D brain tissue architecture. These models can incorporate multiple cell types, including neurons, astrocytes, and microglia, creating a microenvironment that closely resembles the brain\u2019s complexity. Bioengineering approaches allow researchers to better replicate cell\u2013cell interactions, neuronal connectivity, and disease-related phenotypes. Both 2D and 3D models have their advantages and limitations. While 2D cultures provide simplicity and scalability for high-throughput screening and basic processes, 3D models offer enhanced physiological relevance and better replicate disease phenotypes. Integrating findings from both model systems can provide a better understanding of NDs, ultimately aiding in the development of novel therapeutic strategies. Here, we review existing 2D and 3D in vitro models for the study of PD and AD.<\/jats:p>","DOI":"10.3390\/ijms26020620","type":"journal-article","created":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T09:49:17Z","timestamp":1736761757000},"page":"620","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Two- and Three-Dimensional In Vitro Models of Parkinson\u2019s and Alzheimer\u2019s Diseases: State-of-the-Art and Applications"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5148-8796","authenticated-orcid":false,"given":"Cristina","family":"Solana-Manrique","sequence":"first","affiliation":[{"name":"Departamento de Gen\u00e9tica, Facultad de Ciencias Biol\u00f3gicas, Universidad de Valencia, Calle Doctor Moliner 50, 46100 Burjassot, Spain"},{"name":"Instituto Universitario de Biotecnolog\u00eda y Biomedicina (BIOTECMED), Universidad de Valencia, Calle Doctor Moliner 50, 46100 Burjassot, Spain"},{"name":"Departamento de Fisioterapia, Facultad de Ciencias de la Salud, Universidad Europea de Valencia, Paseo de la Alameda 7, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5811-0005","authenticated-orcid":false,"given":"Ana Mar\u00eda","family":"S\u00e1nchez-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Instituto de Materiales Avanzados (INAM), Universidad de Jaume I, Avda Sos Banyat s\/n, 12071 Castell\u00f3n de la Plana, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7193-2532","authenticated-orcid":false,"given":"Nuria","family":"Paricio","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica, Facultad de Ciencias Biol\u00f3gicas, Universidad de Valencia, Calle Doctor Moliner 50, 46100 Burjassot, Spain"},{"name":"Instituto Universitario de Biotecnolog\u00eda y Biomedicina (BIOTECMED), Universidad de Valencia, Calle Doctor Moliner 50, 46100 Burjassot, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0939-7721","authenticated-orcid":false,"given":"Silvia","family":"Mu\u00f1oz-Descalzo","sequence":"additional","affiliation":[{"name":"Instituto Universitario de Investigaciones Biom\u00e9dicas y Sanitarias (IUIBS), Universidad Las Palmas de Gran Canaria (ULPGC), Paseo Blas Cabrera Felipe \u201cF\u00edsico\u201d 17, 35016 Las Palmas de Gran Canaria, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/539179a","article-title":"Neurodegenerative diseases","volume":"539","author":"Heemels","year":"2016","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.cell.2022.12.032","article-title":"Hallmarks of neurodegenerative diseases","volume":"186","author":"Wilson","year":"2023","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Kesidou, E., Theotokis, P., Damianidou, O., Boziki, M., Konstantinidou, N., Taloumtzis, C., Sintila, S.-A., Grigoriadis, P., Evangelopoulos, M.E., and Bakirtzis, C. 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