Sinapsitik mielinara: Autismoaren espektroko nahastearen mekanismo integratzaileak

Abstract

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder of high genetic etiology, affecting approximately 1.5–2% of the global population. While very comprehensive research has established that mutations in synaptogenesis and synaptic function, particularly in genes such as Shank3 and Chd8, are crucial, the latest evidence indicates that ASD etiology also involves significant disturbances in glial biology, particularly in oligodendrocyte differentiation and myelination. This review synthesises current evidence for how common and rare ASD-associated variants affect neuronal function, oligodendrocyte precursor cell (OPC) differentiation, and the formation of mature myelinating oligodendrocytes. Shank3 mutations are reported to impair myelin ultrastructure and gene expression, and loss-of-function mutations in Chd8 result in region-specific, severe disruption of OPC maturation and white matter development. Moreover, recent work further indicates the engagement of abnormal bidirectional communication between OPCs and parvalbumin-positive interneurons, via GABA-B receptors and cytokines like TWEAK, in the pathogenesis of ASD. By integrating glial and neuronal processes, the present review offers a more comprehensive model of ASD pathophysiology and points to new directions for glia-targeted therapeutic approaches towards myelination restoration and functional connectivity improvements.