The Down-Expression of ACE and IDE Exacerbates Exogenous Amyloid-β Neurotoxicity in CB2R-/- Mice
| Autor: | Lin Wang, Qun Wang, Fang-Xiao Shi, Qing Tian, Xin-Wen Zhou, Yun Cao, Li-Kai Yu, Jian-Zhi Wang, Man Li, Wei-Qi Xu, Na Li |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Agonist Proteomics medicine.medical_specialty Cannabinoid receptor medicine.drug_class Long-Term Potentiation Down-Regulation Mice Transgenic Nerve Tissue Proteins Peptidyl-Dipeptidase A Insulysin Statistics Nonparametric Receptor Cannabinoid CB2 03 medical and health sciences Glutamatergic Mice 0302 clinical medicine Internal medicine Cell Line Tumor medicine Insulin-degrading enzyme Animals Senile plaques Maze Learning Injections Intraventricular Amyloid beta-Peptides biology Chemistry General Neuroscience Neurotoxicity Antagonist Membrane Proteins Angiotensin-converting enzyme General Medicine medicine.disease Electric Stimulation Peptide Fragments Mice Inbred C57BL Psychiatry and Mental health Clinical Psychology Disease Models Animal 030104 developmental biology Endocrinology biology.protein Neurotoxicity Syndromes Geriatrics and Gerontology 030217 neurology & neurosurgery |
| Zdroj: | Journal of Alzheimer's disease : JAD. 64(3) |
| ISSN: | 1875-8908 |
| Popis: | Alzheimer's disease (AD) is characterized by neuritic plaques and neurofibrillary tangles. It is reported that enzymatic degradation of amyloid-β (Aβ) plays a pivotal role in Aβ accumulation and type-2 cannabinoid receptor (CB2R) participates in Aβ processing in the brain; however, the underlying mechanisms remain unclear. We determined that Aβ degradation-related proteins are significantly different between CB2R-/- mice and wild-type (WT) mice via proteomic analysis. Moreover, the data demonstrated that the angiotensin converting enzyme (ACE) and insulin-degrading enzyme (IDE) levels are substantially attenuated, and the Aβ level is significantly enhanced in CB2R-/--Aβ1 - 42 mice compared with that of WT-Aβ1 - 42 mice. Furthermore, Aβ-mediated synaptic dysfunction, the loss of memory associated proteins, and the suppression of glutamatergic transmission are more severe in CB2R-/--Aβ1 - 42 mice than that in WT-Aβ1 - 42 mice. CB2R activation could decrease Aβ1 - 40 and Aβ1 - 42 levels and enhance ACE and IDE levels with its selective agonist JWH133; however, AM630 (CB2R antagonist) abrogates all changes induced by JWH133 in N2a cells with AβPP overexpression. Taken together, our study demonstrated that the deletion of CB2R reduces exogenous Aβ degradation and aggravates the toxicity of Aβ via the reduction of ACE and IDE, which suggests that CB2R is involved in the onset of AD and a potential therapeutic target for AD. |
| Databáze: | OpenAIRE |
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