Regulation of aberrant proteasome activity re-establishes plasticity and long-term memory in an animal model of Alzheimer's disease.
FASEB J
; 34(7): 9466-9479, 2020 07.
Article
em En
| MEDLINE
| ID: mdl-32459037
ABSTRACT
Reduced retrograde memory performance at the cognitive level and aggregation/deposition of amyloid beta (Aß) in the brain at the cellular level are some of the hallmarks of Alzheimer's Disease (AD). A molecular system that participates in the removal of proteins with an altered conformation is the Ubiquitin-Proteasome System (UPS). Impairments of the UPS in wild-type (WT) mice lead to defective clearance of Aß and prevent long-term plasticity of synaptic transmission. Here we show data whereby in contrast to WT mice, the inhibition of proteasome-mediated protein degradation in an animal model of AD by MG132 or lactacystin restores impaired activity-dependent synaptic plasticity and its associative interaction, synaptic tagging and capture (STC) in vitro, as well as associative long-term memory in vivo. This augmentation of synaptic plasticity and memory is mediated by the mTOR pathway and protein synthesis. Our data offer novel insights into the rebalancing of proteins relevant for synaptic plasticity which are regulated by UPS in AD-like animal models. In addition, the data provide evidence that proteasome inhibitors might be effective in reinstating synaptic plasticity and memory performance in AD, and therefore offer a new potential therapeutic option for AD treatment.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Complexo de Endopeptidases do Proteassoma
/
Modelos Animais de Doenças
/
Memória de Longo Prazo
/
Doença de Alzheimer
/
Leupeptinas
/
Transtornos da Memória
/
Plasticidade Neuronal
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
FASEB J
Assunto da revista:
BIOLOGIA
/
FISIOLOGIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Singapura