title: Cannabidiol promotes amyloid precursor protein ubiquitination and reduction of beta amyloid expression in SHSY5YAPP+ cells through PPARγ involvement.
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 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.
authors.affiliation: Department of Physiology and Pharmacology 'Vittorio Erspamer', SAPIENZA University of Rome, P.le A. Moro, 5, 00185, Rome, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Scuderi
authors.forename: Luca
authors.initials: L
authors.lastname: Steardo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Esposito
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D002185:Cannabidiol / Q000494:pharmacology*; D002460:Cell Line; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D047495:PPAR gamma / Q000378:metabolism*; D054875:Ubiquitination; D015854:Up-Regulation
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D047495:PPAR gamma; D002185:Cannabidiol
keywords: APP ubiquitination; PPARγ; SHSY5YAPP+; cannabidiol