title: 4'-Chlorodiazepam is neuroprotective against amyloid-beta through the modulation of survivin and bax protein expression in vitro.
abstract: The translocator protein of 18kDa (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 1nM and 10nM. 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.
authors.affiliation: Laboratório de Interação Neuro-Humoral, Department of Physiology, ICBS, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Sarmento Leite, 500, 90050-170 Porto Alegre, RS, Brazil; Instituto Cajal - CSIC, Avenida Doctor Arce, 37, 28002 Madrid, Spain. Electronic address: brunoarbo@gmail.com.
authors.forename: B D
authors.initials: BD
authors.lastname: Arbo
authors.affiliation: Laboratório de Interação Neuro-Humoral, Department of Physiology, ICBS, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Sarmento Leite, 500, 90050-170 Porto Alegre, RS, Brazil; Instituto Cajal - CSIC, Avenida Doctor Arce, 37, 28002 Madrid, Spain.
authors.forename: C V
authors.initials: CV
authors.lastname: Marques
authors.affiliation: Instituto Cajal - CSIC, Avenida Doctor Arce, 37, 28002 Madrid, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Ruiz-Palmero
authors.affiliation: Instituto Cajal - CSIC, Avenida Doctor Arce, 37, 28002 Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Ortiz-Rodriguez
authors.affiliation: Instituto Cajal - CSIC, Avenida Doctor Arce, 37, 28002 Madrid, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Ghorbanpoor
authors.affiliation: Instituto Cajal - CSIC, Avenida Doctor Arce, 37, 28002 Madrid, Spain.
authors.forename: M A
authors.initials: MA
authors.lastname: Arevalo
authors.affiliation: Instituto Cajal - CSIC, Avenida Doctor Arce, 37, 28002 Madrid, Spain.
authors.forename: L M
authors.initials: LM
authors.lastname: Garcia-Segura
authors.affiliation: Laboratório de Interação Neuro-Humoral, Department of Physiology, ICBS, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Sarmento Leite, 500, 90050-170 Porto Alegre, RS, Brazil.
authors.forename: M F
authors.initials: MF
authors.lastname: Ribeiro
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D001570:Benzodiazepinones / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000633:toxicity*; D000077022:Survivin; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis*
chemical_list: D016229:Amyloid beta-Peptides; C494826:BAX protein, human; C107489:BIRC5 protein, human; D001570:Benzodiazepinones; D051034:Inhibitor of Apoptosis Proteins; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D000077022:Survivin; C078592:amyloid beta-protein (1-40); D051028:bcl-2-Associated X Protein; C028513:4'-chlorodiazepam
keywords: Alzheimer׳s disease; Apoptosis; Steroidogenesis; Steroids; Translocator protein (TSPO)