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Home > The Down-Expression of ACE and IDE Exacerbates Exogenous Amyloid-β Neurotoxicity in CB2R-/- Mice.

TitleThe Down-Expression of ACE and IDE Exacerbates Exogenous Amyloid-β Neurotoxicity in CB2R-/- Mice.
Publication TypeJournal Article
Year of Publication2018
AuthorsWang, L, Shi, F-X, Xu, W-Q, Cao, Y, Li, N, Li, M, Wang, Q, Wang, J-Z, Tian, Q, Yu, L-K, Zhou, X-W
JournalJ Alzheimers Dis
Volume64
Issue3
Pagination957-971
Date Published2018
ISSN1875-8908
Abstract

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.

DOI10.3233/JAD-180142
Alternate JournalJ. Alzheimers Dis.
PubMed ID29991137
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Source URL: https://www.j-alz.com/content/down-expression-ace-and-ide-exacerbates-exogenous-amyloid-%CE%B2-neurotoxicity-cb2r-mice