Autism Spectrum Disorder: Neurodevelopmental Risk Factors, Biological Mechanism, and Precision Therapy.

Abstract

Autism spectrum disorder (ASD) is a heterogeneous, behaviorally defined neurodevelopmental disorder. Over the past two decades, the prevalence of autism spectrum disorders has progressively increased, however, no clear diagnostic markers and specifically targeted medications for autism have emerged. As a result, neurobehavioral abnormalities, neurobiological alterations in ASD, and the development of novel ASD pharmacological therapy necessitate multidisciplinary collaboration. In this review, we discuss the development of multiple animal models of ASD to contribute to the disease mechanisms of ASD, as well as new studies from multiple disciplines to assess the behavioral pathology of ASD. In addition, we summarize and highlight the mechanistic advances regarding gene transcription, RNA and non-coding RNA translation, abnormal synaptic signaling pathways, epigenetic post-translational modifications, brain-gut axis, immune inflammation and neural loop abnormalities in autism to provide a theoretical basis for the next step of precision therapy. Furthermore, we review existing autism therapy tactics and limits and present challenges and opportunities for translating multidisciplinary knowledge of ASD into clinical practice.