From molecules to models: A holistic review of autism spectrum disorder mechanisms and research tools

Authors

Sriya Gullapalli, The University of Texas Rio Grande ValleyFollow
Lois Baldado, The University of Texas Rio Grande ValleyFollow
Megan W. Szobody, The University of Texas Rio Grande ValleyFollow
Anesu K. Murambadoro, The University of Texas Rio Grande ValleyFollow
Kevin Garcia Valdez, The University of Texas Rio Grande ValleyFollow
Arjun Bellamkonda, The University of Texas Rio Grande ValleyFollow
Daniela Gonzalez, The University of Texas Rio Grande ValleyFollow
Usman Ghumman
Nikhilesh Anand, The University of Texas Rio Grande ValleyFollow
Kelsey A. Potter-Baker, The University of Texas Rio Grande ValleyFollow
Bharathi Gadad, The University of Texas Rio Grande ValleyFollow

Document Type

Article

Publication Date

12-2025

Abstract

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by persistent deficits in social communication and interaction, as well as restricted, repetitive patterns of behavior, interests, or activities. These features are associated with atypical early brain development and connectivity. While ASD has been traditionally associated with molecular genetic alterations, recent research highlights the significant contribution of various environmental factors to the pathophysiology of the disorder. Pathogenic genetic variations in key regulatory genes remain central to ASD risk; however, environmental influences such as advanced maternal or paternal age, poor maternal health during pregnancy, gestational diabetes mellitus, alterations in the early-life gut microbiome, and other perinatal or early childhood environmental exposures have all been associated with an increased likelihood of developing ASD. This review synthesizes recent advances in our understanding of ASD by providing a comprehensive analysis of the disorder's diverse pathophysiological mechanisms from multiple perspectives. Specifically, this paper discusses neurophysiological, behavioral, and post-mortem findings, and explores the utility of widely used animal models in ASD research. Particular attention is given to dysregulation of key metabolic pathways and the role of the gut-brain axis in ASD. The review also evaluates both established and emerging pharmacotherapeutic approaches, highlighting significant cellular, histological, and behavioral alterations associated with ASD. Collectively, these insights provide a foundation for developing novel tools to understand the molecular pathways of these genes and its implication of novel therapeutic opportunities for individuals with ASD.

Comments

http://creativecommons.org/licenses/by-nc-nd/4.0/

Recommended Citation

Gullapalli, S., Baldado, L., Szobody, M. W., Murambadoro, A. K., Valdez, K. G., Bellamkonda, A., ... & Gadad, B. S. (2025). From molecules to models: A holistic review of autism spectrum disorder mechanisms and research tools. Neurobiology of Disease, 107187. https://doi.org/10.1016/j.nbd.2025.107187

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

Publication Title

Neurobiology of Disease

DOI

10.1016/j.nbd.2025.107187

Academic Level

faculty

Mentor/PI Department

Medical Education