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REVIEW ARTICLE
Bridging molecular mechanisms and therapeutic

innovations: The role of brain organoids in
neurodevelopmental disorder research

Moawiah M. Naffaa *
1,2
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
*Corresponding author: Moawiah M. Naffaa (moawiah.naffaa@duke.edu)

Citation: Naffaa MM. Bridging Abstract
molecular mechanisms and
therapeutic innovations: The
role of brain organoids in This article examines the role of brain organoids in understanding neurodevelopmental
neurodevelopmental disorder disorders (NDDs), including autism spectrum disorder, intellectual disabilities,
research. Organoid Res. and schizophrenia, which arise from disruptions in the complex processes of brain
2025;1(3):025100010.
doi: 10.36922/OR025100010 development. The transformative potential of human pluripotent stem cell-derived
brain organoids as models for investigating the molecular mechanisms underlying
Received: March 4, 2025 NDDs and their implications for therapeutic innovation is explored. By simulating
1st revised: April 11, 2025 critical stages of human brain development – such as neurulation, neurogenesis, and
2nd revised: April 20, 2025 gliogenesis – organoids provide a physiologically relevant platform to investigate
cellular diversity, synaptic connectivity, and neuronal circuit formation. Advanced
Accepted: May 12, 2025 methodologies, including single-cell RNA sequencing and chromatin accessibility
Published online: May 29, 2025 profiling, are utilized to dissect lineage-specific gene expression patterns and
Copyright: © 2025 Author(s). regulatory mechanisms within organoids. In addition, metabolic profiling and
This is an Open-Access article functional assessments comprehensively evaluate neuronal maturation, synaptic
distributed under the terms of the plasticity, and cellular interactions, addressing the limitations of traditional two-
Creative Commons Attribution
License, permitting distribution, and dimensional cultures. This article also examines the influence of environmental
reproduction in any medium, which factors, such as viral infections, by utilizing organoid models to simulate host-
provided that the original work is pathogen interactions and assess their impact on neural progenitor function and
properly cited. cortical development. The integration of machine learning and innovative culture
Publisher’s Note: AccScience systems, including microfluidic and vascularized models, enhances the physiological
Publishing remains neutral with regard relevance and reproducibility of brain organoid research. This review highlights the
to jurisdictional claims in published
maps and institutional affiliations. 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

1. Introduction have provided valuable insights into neurodevelopmental
mechanisms, it is crucial to note that significant species-
Human brain development is a highly intricate and tightly specific differences exist. These differences are evident in
regulated process that unfolds through multiple stages, brain size, cytoarchitecture, and cellular composition.
2
during which various cell types perform specialized Rodent brains are relatively small and feature smooth,
functions. While animal models, particularly rodents, lissencephalic structures, whereas human brains are larger
1

Volume 1 Issue 3 (2025) 1 doi: 10.36922/OR025100010