Journal
ACS CHEMICAL NEUROSCIENCE
Volume 6, Issue 5, Pages 695-700Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acschemneuro.5b00068
Keywords
Translation; proteolysis; amyloid beta; mTOR; protein turnover; metabolic labeling pulse-chase
Funding
- National Institutes of Health [NS066583, AG040975]
- Wake Forest University Health Sciences venture funds
- Roena B. Kulynych Center for Memory and Cognition Research
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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 (A beta), 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 A beta effects on long-term synaptic plasticity.
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