title: Trans-crocetin improves amyloid-β degradation in monocytes from Alzheimer's Disease patients.
abstract: Herbal medicines have been recently employed in research and clinical studies for the potential treatment of behavioral and psychological symptoms associated with Alzheimer's Disease (AD) and other types of dementia. The present study investigates the effect of trans-crocetin, an active constituent of Crocus sativus L., to restore in vitro the reduced ability of AD patients' monocytes to degrade amyloid-β(1-42)(Aβ42). CD14+monocytes from 22 sporadic AD patients with moderate cognitive impairment were isolated; then, the role of trans-crocetin, purified from saffron extracts, was evaluated in terms of Aβ42degradation rate through flow cytometry, as well as expression of cathepsin B by Western blotting. We observed that low micromolar doses of trans-crocetin enhanced Aβ42degradation in AD monocytes through the upregulation of the lysosomal protease cathepsin B. CA074Me, a potent and selective cathepsin B inhibitor, counteracted such trans-crocetin-induced effect. These data suggest that the carotenoid trans-crocetin improves in vitro the clearance of Aβ42through the involvement of cathepsin B, and this could be of value in developing a new anti-amyloid strategy in AD.
authors.affiliation: Istituto di Ricerca Traslazionale per l'Apparato Locomotore Nicola Cerulli, LPMRI, Arezzo, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Tiribuzi
authors.affiliation: Dipartimento di Scienze Chirurgiche e Biomediche, Università di Perugia, Perugia, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Crispoltoni
authors.affiliation: Facoltà Dipartimentale di Medicina e Chirurgia, Università Campus Bio-Medico di Roma, Rome, Italy; Laboratorio di Neurochimica dei Lipidi, Centro Europeo di Ricerca sul Cervello (CERC) - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Santa Lucia, Rome, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Chiurchiù
authors.affiliation: Laboratorio di Neurogenetica, Centro Europeo di Ricerca sul Cervello (CERC) - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Santa Lucia, Rome, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Casella
authors.affiliation: Laboratorio di Neurogenetica, Centro Europeo di Ricerca sul Cervello (CERC) - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Santa Lucia, Rome, Italy.
authors.forename: Celeste
authors.initials: C
authors.lastname: Montecchiani
authors.affiliation: Dipartimento di Scienze Agrarie, Alimentari ed Ambientali, Università di Perugia, Perugia, Italy.
authors.forename: Alberto Marco
authors.initials: AM
authors.lastname: Del Pino
authors.affiliation: Facoltà Dipartimentale di Medicina e Chirurgia, Università Campus Bio-Medico di Roma, Rome, Italy; Laboratorio di Neurochimica dei Lipidi, Centro Europeo di Ricerca sul Cervello (CERC) - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Santa Lucia, Rome, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Maccarrone
authors.affiliation: Dipartimento di Scienze Agrarie, Alimentari ed Ambientali, Università di Perugia, Perugia, Italy.
authors.forename: Carlo Alberto
authors.initials: CA
authors.lastname: Palmerini
authors.affiliation: Laboratorio di Neurologia Clinica e Comportamentale, IRCCS Santa Lucia, Rome, Italy; Dipartimento di Medicina dei Sistemi, Università di Roma "Tor Vergata", Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Caltagirone
authors.affiliation: Department of Clinical Neuroscience, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Kawarai
authors.affiliation: Fondazione GeBiSa, Perugia, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Orlacchio
authors.affiliation: Dipartimento di Scienze Chirurgiche e Biomediche, Università di Perugia, Perugia, Italy; Laboratorio di Neurogenetica, Centro Europeo di Ricerca sul Cervello (CERC) - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Santa Lucia, Rome, Italy. Electronic address: a.orlacchio@hsantalucia.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Orlacchio
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000704:Analysis of Variance; D000975:Antioxidants / Q000627:therapeutic use*; D002338:Carotenoids / Q000627:therapeutic use*; D002401:Cathepsin B / Q000378:metabolism; D003072:Cognition Disorders / Q000209:etiology; D027622:Crocus / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D059748:Proteolysis / Q000187:drug effects*; D014801:Vitamin A / Q000031:analogs & derivatives
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D018950:Lipopolysaccharide Receptors; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C487773:trans-sodium crocetinate; D014801:Vitamin A; D002338:Carotenoids; D002401:Cathepsin B
keywords: Alzheimer's Disease; Aβ(42) degradation; Cathepsin B; Crocus sativus L.; Monocytes; Trans-crocetin