The role of leptin in the sporadic form of Alzheimer's disease. Interactions with the adipokines amylin, ghrelin and the pituitary hormone prolactin

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• 作者：Jaume Folch^a ; ^c ; Ivá ; n Patraca^a ; ^c ; Nohora Martí ; nez^a ; ^c ; Ignacio Pedró ; s^a ; ^b ; Dmitry Petrov^b ; ^c ; Miren Ettcheto^b ; ^c ; Sonia Abad^b ; ^c ; Miguel Marin^f ; Carlos Beas-Zarate^d ; ^e ; Antoni Camins^b ; ^c ; ^f ; ^{camins@ub.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Leptin ; Amylin ; Ghrelin ; Prolactin ; Insulin receptor ; High-fat diet ; Obesity ; Hippocampus ; Alzheimer's disease ; PGC-1伪 ; mTOR
• 刊名：Life Sciences
• 出版年：2015
• 出版时间：1 November 2015
• 年：2015
• 卷：140
• 期：Complete
• 页码：19-28
• 全文大小：1234 K

文摘

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.