Animal studies reveal downregulation of the Beclin-1 autophagy pathway as shared mechanism in Autism Spectrum Disorder: a systematic review and meta-analysis.

Scientists reviewed 192 animal studies to understand how autism affects the brain at a cellular level. They found that a biological process called autophagy (the brain's way of cleaning up damaged cells) is consistently disrupted in autism models. Specifically, a protein called Beclin-1 was reduced across all studies. This suggests autophagy problems might be a common feature of autism, which could help develop new treatments.

This comprehensive meta-analysis examined mTOR signaling pathway dysregulation across 192 animal studies of autism spectrum disorder (ASD). The research investigated diverse genetic and environmental animal models to identify common biological mechanisms in ASD. Results revealed significant alterations in multiple mTOR pathway-related proteins, with effects varying by species, sex, age, and brain region. Most notably, Beclin-1, a key autophagy protein, showed consistent downregulation across all subgroups examined.

The findings support mTOR pathway dysregulation as a shared mechanism in ASD and highlight autophagy dysfunction as a consistent feature, potentially offering new directions for biomarker development and therapeutic targets.

Findings suggest autophagy dysfunction, particularly Beclin-1 downregulation, as potential biomarker for ASD. Results support investigating mTOR pathway modulators and autophagy enhancers as therapeutic targets. However, translation from animal models to human applications requires further clinical validation.

Study limited to animal models, which may not fully translate to human autism. Sample sizes of individual studies within the meta-analysis not reported. Heterogeneity across different animal models and methodologies may affect generalizability of findings.

Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental condition with complex etiology, involving genetic and environmental influences on brain development and behavior. Dysregulation of mammalian target of rapamycin (mTOR) signaling alters neuronal growth and synaptic plasticity, and has emerged as a potential underlying pathway in ASD. To investigate mTOR dysregulation as a common mechanism in ASD, we performed a systematic review, and a meta-analysis of 192 studies examining mTOR signaling in diverse genetic and environmental animal models. Our random-effects model identified significant alterations in mTOR pathway-related proteins.

For several proteins (p-AKT, PTEN, p-mTOR, p-EIF4e, LC3-II, p-S6K and p-S6), subgroup analyses revealed clear species-, sex-, age-, or brain region-specific effects. Interestingly, Beclin-1 was consistently downregulated across all subgroups. Our findings support mTOR-pathway dysregulation in ASD. The observed consistent downregulation of Beclin-1 highlights autophagy as a common mechanism, and provides new leads for novel ASD biomarker and treatment development.