Affiliations: [a] Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| [b] Neurobiology Programme, Life Sciences Institute, National University of Singapore, Singapore
| [c] Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China
| [d] Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Correspondence:
[*]
Correspondence to: Sreedharan Sajikumar, Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore. E-mail: phssks@nus.edu.sg; ORCID iD: 0000-0002-5761-8982 and Kumar Krishna-K, School of Advanced Studies, University of Tyumen, Tyumen 625 000, Russia. E-mail: krisdna@gmail.com.
Note: [1] Current affiliation: School of Advanced Studies, University of Tyumen, Tyumen, Russia.
Abstract: 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, hippocampus, lactacystin, long-term potentiation, MG132, protein degradation, proteostasis, synaptic plasticity, ubiquitin-proteasome system
