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Impaired Activity-Regulated Proteostasis: A Shared Mechanism in Neurodevelopmental Disorders
1Department of Pharmacology, Weill Cornell Medicine, Cornell University, New York, New York, USA.
Proteostasis, the regulation of protein levels, is disrupted in neurodevelopmental disorders (NDDs). Restoring the link between neuronal activity and proteostasis can improve cognitive function in NDDs.
Area of Science:
- Neuroscience
- Cell Biology
- Genetics
Background:
- Proteostasis maintains cellular protein balance.
- Neuronal activity dynamically regulates proteostasis to support synaptic plasticity.
- Dysregulated proteostasis in neurodevelopmental disorders (NDDs) impairs synaptic plasticity and cognitive function.
Purpose of the Study:
- To establish activity-regulated proteostasis failure as a common vulnerability across NDDs.
- To investigate the therapeutic potential of restoring proteostasis in NDDs.
Main Methods:
- Review of existing literature on proteostasis and NDDs.
- Analysis of molecular and cognitive outcomes in NDD models.
Main Results:
- Failure of activity-regulated proteostasis is a shared characteristic of NDDs, irrespective of genetic origin.
- Targeting protein synthesis or degradation alone is insufficient to restore function.
- Restoring the coupling between neuronal activity and proteostasis rescues molecular and cognitive deficits in NDDs.
Conclusions:
- Activity-regulated proteostasis is crucial for neuronal function and cognitive health.
- Therapeutic strategies targeting the activity-proteostasis axis hold promise for NDD treatment.
- Further research into disease biology and novel therapeutic interventions is warranted.
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