Canna~Fangled Abstracts

Cannabidiol Promotes Amyloid Precursor Protein Ubiquitination and Reduction of Beta Amyloid Expression in SHSY5YAPP+ Cells Through PPARγ Involvement.

By November 30, 2013 No Comments
[Epub ahead of print]

pm8Cannabidiol Promotes Amyloid Precursor Protein Ubiquitination and Reduction of Beta Amyloid Expression in SHSY5YAPP+ Cells Through PPARγ Involvement.

Source

Department of Physiology and Pharmacology ‘Vittorio Erspamer’, SAPIENZA University of Rome, P.le A. Moro, 5, 00185, Rome, Italy.

Abstract

The amyloidogenic cascade is regarded as a key factor at the basis of Alzheimer’s disease (AD) pathogenesis. The aberrant cleavage of amyloid precursor protein (APP) induces an increased production and a subsequent aggregation of beta amyloid (Aβ) peptide in limbic and association cortices. As a result, altered neuronal homeostasis and oxidative injury provoke tangle formation with consequent neuronal loss. Cannabidiol (CBD), a Cannabis derivative devoid of psychotropic effects, has attracted much attention because it may beneficially interfere with several Aβ-triggered neurodegenerative pathways, even though the mechanism responsible for such actions remains unknown. In the present research, the role of CBD was investigated as a possible modulating compound of APP processing in SHSY5YAPP+ neurons. In addition, the putative involvement of peroxisome proliferator-activated receptor-γ (PPARγ) was explored as a candidate molecular site responsible for CBD actions. Results indicated the CBD capability to induce the ubiquitination of APP protein which led to a substantial decrease in APP full length protein levels in SHSY5YAPP+with the consequent decrease in Aβ production. Moreover, CBD promoted an increased survival of SHSY5YAPP+neurons, by reducing their long-term apoptotic rate. Obtained results also showed that all, here observed, CBD effects were dependent on the selective activation of PPARγ. Copyright © 2013 John Wiley & Sons, Ltd.
Copyright © 2013 John Wiley & Sons, Ltd.

KEYWORDS:

APP ubiquitination, PPARγ, SHSY5YAPP+, cannabidiol

PMID:

 

24288245

 

[PubMed – as supplied by publisher]
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