Autism: Insights into Effects of Mutations in Neuronal Proteins

KREMS, Austria - Jan. 29, 2025 - PRLog -- A recent study has uncovered how specific genetic mutations in α2δ-1 and α2δ-3 proteins linked to autism spectrum disorders (ASD) alter neuronal functionality. These mutations significantly reduce the proteins' membrane expression and synaptic targeting but do not impair calcium channel activity or trans-synaptic signalling. Conducted at Karl Landsteiner University of Health Sciences (KL Krems) within the research focus Mental Health and Neuroscience, the research provides a fresh perspective on how subtle disruptions in protein function may influence synapse formation and neuronal networks. The results underscore the need for new experimental tools and might offer new angles for developing targeted treatments addressing the complex biology of ASD.

Autism spectrum disorder, a complex neurodevelopmental condition, affects millions worldwide and is marked by challenges in communication, social behaviour, and repetitive actions. A significant proportion of ASD cases are linked to genetic factors, with mutations in the CACNA2D1 and CACNA2D3 genes — which encode α2δ-1 and α2δ-3 proteins—emerging as critical players. These proteins regulate calcium channels, synapse formation, and neuronal connectivity, yet their exact role in ASD has remained elusive. To bridge this gap, KL Krems' Division of Physiology embarked on a comprehensive study to explore cellular pathophysiological mechanisms of mutations in these genes.

A Subtle Disruption

„These findings redefine how we understand the role of α2δ proteins in brain development", says Prof. Dr. Gerald Obermair, Head of the Division of Physiology at KL Krems. His team revealed that two specific mutations — p.R351T in α2δ-1 and p.A275T in α2δ-3 — reduce the presence of these proteins at neuronal membranes, thereby disrupting the synaptic localization. „What makes this discovery particularly compelling is that while the mutations don't affect classical calcium channel functions, subtle changes may significantly affect synaptic functions", Sabrin Haddad, M.Sc., first author of the publication and PhD student in the team of Prof. Obermair, adds.

Scientific Contact

Prof. Dr. Gerald Obermair

Division of Physiology

Department of Pharmacology, Physiology and Microbiology

Karl Landsteiner University of Health Sciences

Dr.-Karl-Dorrek-Straße 30

3500 Krems / Austria

T +43 2732 9004 12141

E gerald.obermair@kl.ac.at

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