title: Proteasome inhibition augments new protein accumulation early in long-term synaptic plasticity and rescues adverse Aβ effects on protein synthesis.
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.
authors.affiliation: Department of Neurobiology and Anatomy, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, North Carolina 27157, United States.
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Haynes
authors.affiliation: Department of Neurobiology and Anatomy, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, North Carolina 27157, United States.
authors.forename: Thuy K
authors.initials: TK
authors.lastname: Smith
authors.affiliation: Department of Neurobiology and Anatomy, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, North Carolina 27157, United States.
authors.forename: Collin J
authors.initials: CJ
authors.lastname: Preston
authors.affiliation: Department of Neurobiology and Anatomy, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, North Carolina 27157, United States.
authors.forename: Ashok N
authors.initials: AN
authors.lastname: Hegde
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D006624:Hippocampus / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000187:drug effects / Q000502:physiology*; D015531:Radioimmunoprecipitation Assay
chemical_list: D016229:Amyloid beta-Peptides; D046988:Proteasome Endopeptidase Complex
keywords: Translation; amyloid beta; mTOR; metabolic labeling; protein turnover; proteolysis; pulse-chase