Parkin overexpression ameliorates hippocampal long-term potentiation and -amyloid load in an Alzheimer's disease mouse model
| Autor: | Dongping Huang, Haiyun Suo, Jing Xu, Xiaoqi Hong, Guoqi Zhu, Mei Yu, YingHan Zhuang, Yufang Huang, Zhejin Sheng, MinJuan Bian, Houyan Song, Fang Huang, Jian Fei, Jie Liu, Pan Wang, Thomas Behnisch |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Male
Genetically modified mouse Proteasome Endopeptidase Complex Transcription Genetic Amyloid Ubiquitin-Protein Ligases Transgene Long-Term Potentiation Synaptophysin Gene Expression Mice Transgenic Hippocampus Parkin Amyloid beta-Protein Precursor Mice Ubiquitin Alzheimer Disease mental disorders Genetics Animals Humans Maze Learning Molecular Biology Genetics (clinical) Cerebral Cortex biology Ubiquitination Long-term potentiation General Medicine nervous system diseases Ubiquitin ligase Cell biology Mice Inbred C57BL Disease Models Animal Proteolysis Synaptic plasticity biology.protein Female |
| Zdroj: | Human Molecular Genetics. 23:1056-1072 |
| ISSN: | 1460-2083 0964-6906 |
| DOI: | 10.1093/hmg/ddt501 |
| Popis: | Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by a severe decline of memory performance. A widely studied AD mouse model is the APPswe/PSEN1ΔE9 (APP/PS1) strain, as mice exhibit amyloid plaques as well as impaired memory capacities. To test whether restoring synaptic plasticity and decreasing β-amyloid load by Parkin could represent a potential therapeutic target for AD, we crossed APP/PS1 transgenic mice with transgenic mice overexpressing the ubiquitin ligase Parkin and analyzed offspring properties. Overexpression of Parkin in APP/PS1 transgenic mice restored activity-dependent synaptic plasticity and rescued behavioral abnormalities. Moreover, overexpression of Parkin was associated with down-regulation of APP protein expression, decreased β-amyloid load and reduced inflammation. Our data suggest that Parkin could be a promising target for AD therapy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|