title: The role of leptin in the sporadic form of Alzheimer's disease. Interactions with the adipokines amylin, ghrelin and the pituitary hormone prolactin.
abstract: Leptin (Lep) is emerging as a pivotal molecule involved in both the early events and the terminal phases of Alzheimer's disease (AD). In the canonical pathway, Lep acts as an anorexigenic factor via its effects on hypothalamic nucleus. However, additional functions of Lep in the hippocampus and cortex have been unravelled in recent years. Early events in the sporadic form of AD likely involve cellular level alterations which can have an effect on food intake and metabolism. Thus, AD can be conceivably interpreted as a multiorgan pathology that not only results in a dramatic neuronal loss in brain areas such as the hippocampus and the cortex (ultimately leading to a significant cognitive impairment) but as a disease which also affects body-weight homeostasis. According to this view, body-weight control disruptions are to be expected in both the early- and late-stage AD, concomitant with changes in serum Lep content, alterations in Lep transport across the blood-brain barrier (BBB) and Lep receptor-related signalling abnormalities. Lep is a member of the adipokine family of molecules, while the Lep receptor belongs to the class I cytokine receptors. Since cellular response to adipokine signalling can be either potentiated or diminished as a result of specific ligand-receptor interactions, Lep interactions with other members of the adipokine family including amylin, ghrelin and hormones such as prolactin require further investigation. In this review, we provide a general perspective on the functions of Lep in the brain, with a particular focus on the sporadic AD.
authors.affiliation: Unitats de Bioquímica i Farmacologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, C./ St. Llorenç 21, 43201 Reus, Tarragona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos Tercero, Madrid, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Folch
authors.affiliation: Unitats de Bioquímica i Farmacologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, C./ St. Llorenç 21, 43201 Reus, Tarragona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos Tercero, Madrid, Spain.
authors.forename: Iván
authors.initials: I
authors.lastname: Patraca
authors.affiliation: Unitats de Bioquímica i Farmacologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, C./ St. Llorenç 21, 43201 Reus, Tarragona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos Tercero, Madrid, Spain.
authors.forename: Nohora
authors.initials: N
authors.lastname: Martínez
authors.affiliation: Unitats de Bioquímica i Farmacologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, C./ St. Llorenç 21, 43201 Reus, Tarragona, Spain; Unitat de Farmacologia i Farmacognòsia Facultat de Farmàcia, Institut de Biomedicina (IBUB), Universitat de Barcelona, Barcelona, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Pedrós
authors.affiliation: Unitat de Farmacologia i Farmacognòsia Facultat de Farmàcia, Institut de Biomedicina (IBUB), Universitat de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos Tercero, Madrid, Spain.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Petrov
authors.affiliation: Unitat de Farmacologia i Farmacognòsia Facultat de Farmàcia, Institut de Biomedicina (IBUB), Universitat de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos Tercero, Madrid, Spain.
authors.forename: Miren
authors.initials: M
authors.lastname: Ettcheto
authors.affiliation: Unitat de Farmacologia i Farmacognòsia Facultat de Farmàcia, Institut de Biomedicina (IBUB), Universitat de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos Tercero, Madrid, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Abad
authors.affiliation: Centro de Biotecnología, Universidad Nacional de Loja, Av. Pío Jaramillo Alvarado y Reinaldo Espinosa, La Argelia, Loja, Ecuador.
authors.forename: Miguel
authors.initials: M
authors.lastname: Marin
authors.affiliation: Departamento de Biología Celular y Molecular, C.U.C.B.A., Universidad de Guadalajara and División de Neurociencias, Centro de Investigación Biomédica de Occidente (CIBO), Mexico; Instituto Mexicano del Seguro Social (IMSS), Sierra Mojada 800, Col. Independencia, Guadalajara, Jalisco 44340, Mexico.
authors.forename: Carlos
authors.initials: C
authors.lastname: Beas-Zarate
authors.affiliation: Unitat de Farmacologia i Farmacognòsia Facultat de Farmàcia, Institut de Biomedicina (IBUB), Universitat de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos Tercero, Madrid, Spain; Centro de Biotecnología, Universidad Nacional de Loja, Av. Pío Jaramillo Alvarado y Reinaldo Espinosa, La Argelia, Loja, Ecuador. Electronic address: camins@ub.edu.
authors.forename: Antoni
authors.initials: A
authors.lastname: Camins
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D054439:Ghrelin / Q000378:metabolism*; D006801:Humans; D007031:Hypothalamus / Q000502:physiology; D058228:Islet Amyloid Polypeptide / Q000378:metabolism*; D020738:Leptin / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D008019:Life Style; D009765:Obesity / Q000503:physiopathology; D011388:Prolactin / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D054439:Ghrelin; D058228:Islet Amyloid Polypeptide; D020738:Leptin; D011388:Prolactin
keywords: Alzheimer's disease; Amylin; Ghrelin; High-fat diet; Hippocampus; Insulin receptor; Leptin; Obesity; PGC-1α; Prolactin; mTOR