REVIEW article
Front. Neurosci.
Sec. Neurodevelopment
Volume 19 - 2025 | doi: 10.3389/fnins.2025.1655348
Autism Spectrum Disorder and the role of Nuclear Hormone Receptors: Insights and Therapeutic Implications
Provisionally accepted- Ocugen, Inc., Malvern, United States
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Autism spectrum disorder is a neurological and developmental condition known to impact a person's learning, communication, and interpersonal interactions. Recent research has highlighted the role of nuclear hormone receptors (NHRs) in neurodevelopment and synaptic function, suggesting their potential involvement in ASD pathophysiology. NHRs regulate gene expression that are critical for neural differentiation, plasticity, and metabolic processes. Dysregulation of these receptors can lead to altered neural circuit formation and neurotransmitter imbalances, which are commonly observed in ASD. Understanding the interplay between NHRs and ASD could open new avenues for therapeutic interventions, providing hope for more personalized approaches to managing the disorder. One key receptor is retinoic acid-related orphan receptor-alpha (RORA), which was shown to be reduced in individuals with ASD. Among its numerous functions during development, RORA was shown to regulate the transcription of genes involved in neuronal differentiation, synaptic function, and neuroprotection. Studies have identified that RORA expression is reduced in individuals with ASD, particularly in the prefrontal cortex and cerebellum, affecting transcription of multiple ASD-associated genes. In the present review, we discuss the underlying mechanisms leading to ASD pathophysiology, various treatment modalities, the prospects of the RORA gene therapy approach, and future perspectives.
Keywords: Autism Spectrum Disorder, nHRS, RORA, adeno-associated viral vectors, Gene Therapy
Received: 03 Jul 2025; Accepted: 01 Oct 2025.
Copyright: © 2025 Chintalapally, Rajanala and Upadhyay. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Kalpana Rajanala, kalpana.rajanala@ocugen.com
Arun K Upadhyay, arun@ocugen.com
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.