Drosophila melanogaster as a Model for Autism Spectrum Disorder: Insights into Lifelong Neuronal Vulnerability.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by impaired social communication, restricted interests, and repetitive behaviors. Although traditionally considered a disorder of early brain development, growing evidence indicates that many ASD-associated genes continue to regulate neuronal physiology throughout adulthood. These genes participate in conserved cellular processes involved in synaptic organization, mitochondrial homeostasis, calcium signaling, proteostasis, intracellular trafficking, neuroimmune regulation, and circadian biology, many of which are also implicated in brain aging. This convergence supports the concept that developmental alterations can influence neuronal function long after neural circuits have formed. In this context, the fruit fly Drosophila melanogaster (Drosophila) has emerged as a powerful translational model for investigating the conserved mechanisms linking neurodevelopment and aging. Its high genetic conservation with humans, sophisticated neurogenetic tools, short lifespan, and robust behavioral assays enable longitudinal examination of developmental genetic alterations within a single experimental organism, facilitating mechanistic studies of neuronal function, stress adaptation, and age-dependent behavioral phenotypes. This review examines ASD from the perspective of lifelong neuronal vulnerability, highlighting how genetically diverse ASD-associated genes converge on common biological mechanisms that remain active beyond development. Furthermore, I discuss how Drosophila has advanced our understanding of these conserved pathways and provides a unique experimental platform for investigating how early developmental alterations shape neuronal function across the lifespan.