Synapse and primary cilia dysfunctions in Autism Spectrum Disorders. Avenues to normalize these functions

Area of Science:

• Neuroscience
• Genetics
• Developmental Biology

Background:

• Autism spectrum disorder (ASD) is characterized by complex neurodevelopmental alterations.
• Synaptic and ciliary dysfunction are increasingly recognized as key factors in ASD pathophysiology.

Purpose of the Study:

• To provide an updated review on brain network plasticity in ASD.
• To highlight the roles of synapses and primary non-motile cilia in ASD.

Main Methods:

• Comprehensive literature review of studies published up to February 2024.
• Analysis of data from PubMed and Google Scholar.

Main Results:

• ASD is associated with structural and functional brain abnormalities, including altered synaptic proteins (e.g., neuroligins, neurexins, Shank proteins) and cilia proteins (e.g., IFT-independent kinesins).
• Key findings include reduced dendritic pruning, minicolumnar pathology, altered glutamatergic and GABAergic transmission, and links to genetic ciliopathies.
• Abnormalities in neuronal circuit modification involving synapses and cilia are prevalent in ASD.

Conclusions:

• Clinical heterogeneity in ASD correlates with brain network, synapse, and cilia abnormalities.
• Targeting these pathways presents promising therapeutic research directions, leveraging extended brain plasticity.
• Early ASD detection and further research into synaptic and ciliary mechanisms are crucial.