Alzheimer's disease (AD) is characterized by memory and cognitive deficits that in part are related to a diminished ability to activity-dependent synaptic plasticity. In AD, an attenuated long-term potentiation has been correlated with a deficit of synaptic plasticity-relevant proteins and protein turnover. The ubiquitin-proteasome system (UPS) critically regulates the protein turnover and contributes to dynamic changes of the protein milieu within synapses. In AD, UPS aberration has been implicated in inadequate proteostasis and synaptic malfunction. However, here we show that the inhibition of proteasome-mediated protein degradation by MG132 or lactacystin restored an impaired activity-dependent synaptic plasticity in an AD-like mouse model. In this whole-cell voltage-clamp study, we provided evidence that an amelioration of long-term plasticity by modulating UPS activity in pyramidal neurons.
Keywords: Alzheimer’s disease; MG132; hippocampus; lactacystin; long-term potentiation; protein degradation; proteostasis; synaptic plasticity; ubiquitin-proteasome system.