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Title

4'-Chlorodiazepam is neuroprotective against amyloid-beta through the modulation of survivin and bax protein expression in vitro

AuthorsArbo, B. D.; Marques, C. V.; Ruiz-Palmero, Isabel; Ortiz-Rodriguez, Ana; Ghorbanpoor, Samar; Arévalo, María Ángeles ; García-Segura, Luis M. ; Ribeiro, M. Flavia
KeywordsTranslocator protein (TSPO)
Steroids
Steroidogenesis
Apoptosis
Alzheimer׳s disease
Issue Date1-Feb-2016
PublisherElsevier
CitationBrain Research 1632: 91-97 (2016)
AbstractThe translocator protein of 18 kDa (TSPO) is located in the outer mitochondrial membrane and is involved in the cholesterol transport into the mitochondria and in the regulation of steroidogenesis, mitochondrial permeability transition pore opening and apoptosis. TSPO ligands have been investigated as therapeutic agents that promote neuroprotective effects in experimental models of brain injury and neurodegenerative diseases. The aim of this study was to identify the neuroprotective effects of 4′-chlorodiazepam (4′-CD), a ligand of TSPO, against amyloid-beta (Aβ) in SHSY-5Y neuroblastoma cells and its mechanisms of action. Aβ decreased the viability of SHSY-5Y neuroblastoma cells, while 4′-CD had a neuroprotective effect at the doses of 1 nM and 10 nM. The neuroprotective effects of 4′-CD against Aβ were associated with the inhibition of Aβ-induced upregulation of Bax and downregulation of survivin. In summary, our findings indicate that 4′-CD is neuroprotective against Aβ-induced neurotoxicity by a mechanism that may involve the regulation of Bax and survivin expression.
Publisher version (URL)http://dx.doi.org/10.1016/j.brainres.2015.12.018
URIhttp://hdl.handle.net/10261/199962
DOI10.1016/j.brainres.2015.12.018
ISSN0006-8993
E-ISSN1872-6240
Appears in Collections:(IC) Artículos
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