A perspective on molecular signalling dysfunction, its clinical relevance and therapeutics in autism spectrum disorder

Intellectual disability (ID) and autism spectrum disorder (ASD) are neurodevelopmental disorders that have become a primary clinical and social concern, with a prevalence of 2-3% in the population. Neuronal function and behaviour undergo significant malleability during the critical period of development that is found to be impaired in ID/ASD. Human genome sequencing studies have revealed many genetic variations associated with ASD/ID that are further verified by many approaches, including many mouse and other models. These models have facilitated the identification of fundamental mechanisms underlying the pathogenesis of ASD/ID, and several studies have proposed converging molecular pathways in ASD/ID. However, linking the mechanisms of the pathogenic genes and their molecular characteristics that lead to ID/ASD has progressed slowly, hampering the development of potential therapeutic strategies. This review discusses the possibility of recognising the common molecular causes for most ASD/ID based on studies from the available models that may enable a better therapeutic strategy to treat ID/ASD. We also reviewed the potential biomarkers to detect ASD/ID at early stages that may aid in diagnosis and initiating medical treatment, the concerns with drug failure in clinical trials, and developing therapeutic strategies that can be applied beyond a particular mutation associated with ASD/ID.

Automated summary

Intellectual disability (ID) and autism spectrum disorder (ASD) are neurodevelopmental disorders with a prevalence of 2-3% in the population. Research on genetic variations associated with ID/ASD has progressed, but the understanding of the underlying molecular mechanisms and their connection to the pathogenic genes is still limited. This review explores the potential of identifying common molecular causes for ID/ASD based on available models and discusses biomarkers, drug failures in clinical trials, and therapeutic strategies beyond specific mutations.