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REVIEW ARTICLE

Bridging molecular mechanisms and therapeutic innovations: The role of brain organoids in neurodevelopmental disorder research

Moawiah M. Naffaa1,2*
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1 Department of Psychology and Neuroscience, Duke University, Durham, North Carolina, United States of America
2 Department of Cell Biology, Duke University School of Medicine, Durham, North Carolina, United States of America
OR, 025100010 https://doi.org/10.36922/OR025100010
Received: 4 March 2025 | Revised: 20 April 2025 | Accepted: 12 May 2025 | Published online: 29 May 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

This article examines the role of brain organoids in understanding neurodevelopmental disorders (NDDs), including autism spectrum disorder, intellectual disabilities, and schizophrenia, which arise from disruptions in the complex processes of brain development. The transformative potential of human pluripotent stem cell-derived brain organoids as models for investigating the molecular mechanisms underlying NDDs and their implications for therapeutic innovation is explored. By simulating critical stages of human brain development – such as neurulation, neurogenesis, and gliogenesis – organoids provide a physiologically relevant platform to investigate cellular diversity, synaptic connectivity, and neuronal circuit formation. Advanced methodologies, including single-cell RNA sequencing and chromatin accessibility profiling, are utilized to dissect lineage-specific gene expression patterns and regulatory mechanisms within organoids. In addition, metabolic profiling and functional assessments comprehensively evaluate neuronal maturation, synaptic plasticity, and cellular interactions, addressing the limitations of traditional two-dimensional cultures. This article also examines the influence of environmental factors, such as viral infections, by utilizing organoid models to simulate host-pathogen interactions and assess their impact on neural progenitor function and cortical development. The integration of machine learning and innovative culture systems, including microfluidic and vascularized models, enhances the physiological relevance and reproducibility of brain organoid research. This review highlights the potential use of organoids in elucidating the molecular pathology of NDDs and as platforms for drug discovery and personalized therapeutic screening, ultimately bridging molecular insights with therapeutic applications and underscoring the vital role of brain organoids in advancing the understanding of NDDs and facilitating the development of targeted interventions.

Keywords
Organoids
Neurodevelopmental disorders
Human pluripotent stem cells
Single-cell RNA sequencing
Viral infections
Culture systems
Machine learning
Funding
None.
Conflict of interest
The author declares no conflicts of interest.
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