Unravelling the role of SHANK3 mutations in targeted therapies for autism spectrum disorders

Abstract Autism Spectrum Disorder (ASD) presents a significant challenge due to its complex genetic basis and associated comorbidities. Among the genes implicated in ASD, SHANK3 has been identified as a critical player, affecting synaptic structure and function. This review examines the role of SHANK3 in ASD, highlighting the genetic diversity and the systemic nature of the disorder. Utilizing animal models, studies have uncovered autism-like behaviours and synaptic dysfunctions linked to SHANK3 deficiency, suggesting potential therapeutic targets. Furthermore, the review delves into the specific gene families associated with ASD, emphasizing the dynamic regulation between translation and transcription processes and the impact of mutations on synaptic translation and proteins. Molecular changes in SHANK3-deficient animal models reveal alterations in protein composition, localization, and transcription, particularly affecting the striatum and involving essential proteins and signalling pathways. Therapeutic strategies, including pharmaceutical compounds and genetic restoration, show promise in addressing the neuropsychiatric symptoms and physiological abnormalities observed in SHANK3-deficient mice. This research not only advances our understanding of ASD's neurobiological basis but also underscores the potential of targeted interventions to mitigate symptoms and improve the quality of life for individuals affected by ASD and related disorders.