Gangliosides and Cholesterol: Dual Regulators of Neuronal Membrane Framework in Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with heterogeneous clinical presentation. Diagnosing ASD is complex, and the criteria for diagnosis, as well as the term ASD, have changed during the last decades. Diagnosis is made based on observation and accomplishment of specific diagnostic criteria, while a particular biomarker of ASD does not yet exist. However, studies universally report a disequilibrium in membrane lipid content, pointing to a unique neurolipid signature of ASD. This review sheds light on the possible role of cholesterol and gangliosides, complex membrane glycosphingolipids, in the development of ASD. In addition to maintaining membrane integrity, neuronal signaling, and synaptic plasticity, these lipids play a role in neurotransmitter release and calcium signaling. Evidence linking ASD to lipidome changes includes low cholesterol levels, unusual ganglioside levels, and unique metabolic profiles. ASD symptoms may be mitigated with therapeutic interventions targeting the lipid composition of membranes. However, restoring membrane equilibrium in the central nervous system remains a challenge. This review underscores the need for comprehensive research into lipid metabolism to uncover practical insights into ASD etiology and treatment as lipidomics emerges as a major area in ASD research.