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      Trans-crocetin improves amyloid-β degradation in monocytes from Alzheimer's Disease patients.

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          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 Aβ42 degradation rate through flow cytometry, as well as expression of cathepsin B by Western blotting. We observed that low micromolar doses of trans-crocetin enhanced Aβ42 degradation 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 Aβ42 through the involvement of cathepsin B, and this could be of value in developing a new anti-amyloid strategy in AD.

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          Author and article information

          Journal
          J. Neurol. Sci.
          Journal of the neurological sciences
          Elsevier BV
          1878-5883
          0022-510X
          Jan 15 2017
          : 372
          Affiliations
          [1 ] Istituto di Ricerca Traslazionale per l'Apparato Locomotore Nicola Cerulli, LPMRI, Arezzo, Italy.
          [2 ] Dipartimento di Scienze Chirurgiche e Biomediche, Università di Perugia, Perugia, Italy.
          [3 ] 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.
          [4 ] Laboratorio di Neurogenetica, Centro Europeo di Ricerca sul Cervello (CERC) - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Santa Lucia, Rome, Italy.
          [5 ] Dipartimento di Scienze Agrarie, Alimentari ed Ambientali, Università di Perugia, Perugia, Italy.
          [6 ] Laboratorio di Neurologia Clinica e Comportamentale, IRCCS Santa Lucia, Rome, Italy; Dipartimento di Medicina dei Sistemi, Università di Roma "Tor Vergata", Rome, Italy.
          [7 ] Department of Clinical Neuroscience, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
          [8 ] Fondazione GeBiSa, Perugia, Italy.
          [9 ] 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.
          Article
          S0022-510X(16)30699-2
          10.1016/j.jns.2016.11.004
          27865556
          72581cde-0231-4e1b-8bd3-a57e2753864a
          History

          Alzheimer's Disease,Aβ(42) degradation,Cathepsin B,Crocus sativus L.,Monocytes,Trans-crocetin

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