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Cannabidiol Promotes Amyloid Precursor Protein Ubiquitination and Reduction of Beta Amyloid Expression in SHSY5Y APP+ Cells Through PPARγ Involvement
Author(s) -
Scuderi Caterina,
Steardo Luca,
Esposito Giuseppe
Publication year - 2014
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.5095
Subject(s) - amyloid precursor protein , cannabidiol , chemistry , p3 peptide , amyloid precursor protein secretase , amyloid beta , microbiology and biotechnology , amyloid (mycology) , ubiquitin , biochemistry , alzheimer's disease , biology , medicine , peptide , inorganic chemistry , disease , cannabis , psychiatry , gene
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 SHSY5Y APP+ 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 SHSY5Y APP+ with the consequent decrease in Aβ production. Moreover, CBD promoted an increased survival of SHSY5Y APP+ 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.