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Dynamic Clamp Methods to Investigate Impaired Neuronal Excitability Associated with Autism
Published on: October 17, 2025
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Perturbed proteostasis in autism spectrum disorders.
Susana R Louros1, Emily K Osterweil1
1Centre for Integrative Physiology/Patrick Wild Centre, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh, EH8 9XD, UK.
Journal of Neurochemistry
|July 2, 2016
Summary
Synaptic plasticity and memory depend on protein balance. Disruptions in the ubiquitin proteasome system (UPS) and protein synthesis are linked to autism spectrum disorders (ASD) due to impaired proteostasis.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Synaptic plasticity, crucial for learning and memory, relies on precise regulation of protein synthesis and degradation.
- The ubiquitin proteasome system (UPS) is vital for protein degradation and maintaining cellular homeostasis.
- Imbalances in protein homeostasis (proteostasis) at the synapse are implicated in neurological disorders.
Purpose of the Study:
- To review the role of the UPS in synaptic plasticity at glutamatergic synapses.
- To propose that impaired proteostasis is a common factor in genetic mutations linked to autism spectrum disorders (ASD).
Main Methods:
- Literature review of studies on the UPS, synaptic plasticity, and ASD genetics.
- Analysis of genetic mutations affecting mRNA translation and UPS function.
Main Results:
- Mutations in genes like FMR1 and UBE3A disrupt proteostasis.
- These disruptions impair synaptic plasticity and are associated with ASD and intellectual disability (ASD/ID).
Conclusions:
- Dysfunctional proteostasis at the synapse is a potential common mechanism underlying ASD/ID.
- Compensatory changes in proteostasis may contribute to the neurological symptoms of ASD/ID.
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