Proteasome inhibition augments new protein accumulation early in long-term synaptic plasticity and rescues adverse Aβ effects on protein synthesis

ACS Chemical Neuroscience
Kathryn A HaynesAshok N Hegde

Abstract

Protein degradation plays a critical role in synaptic plasticity, but the molecular mechanisms are not well understood. Previously we showed that proteasome inhibition enhances the early induction part of long-term synaptic plasticity for which protein synthesis is essential. In this study, we tested the effect of proteasome inhibition on protein synthesis using a chemically induced long-lasting synaptic plasticity (cLTP) in the murine hippocampus as a model system. Our metabolic labeling experiments showed that cLTP induction increases protein synthesis and proteasome inhibition enhances the amount of newly synthesized proteins. We then found that amyloid beta (Aβ), a peptide contributing to Alzheimer's pathology and impairment of synaptic plasticity, blocks protein synthesis increased by cLTP. This blockade can be reversed by prior proteasome inhibition. Thus, our work reveals interactions between protein synthesis and protein degradation and suggests a possible way to exploit protein degradation to rescue adverse Aβ effects on long-term synaptic plasticity.

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Citations

May 28, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Kumar Krishna-KSreedharan Sajikumar
Jun 28, 2019·Frontiers in Cellular Neuroscience·Man-Man WangFeng Zhang

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