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.
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.
Life Sci. 2015 Nov 1;140:19-28. doi: 10.1016/j.lfs.2015.05.002. Epub 2015 May 19.
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.
瘦素（Lep）作为一种关键分子，参与阿尔茨海默病（AD）的早期事件和终末阶段。在经典途径中，瘦素通过对下丘脑核的作用作为一种厌食因子。然而，近年来在海马体和皮质中发现了瘦素的其他功能。散发性 AD 的早期事件可能涉及细胞水平的改变，这些改变可能会影响食物摄入和代谢。因此，AD 可以被认为是一种多器官病理学，不仅导致大脑区域（如海马体和皮质）神经元大量丧失（最终导致显著的认知障碍），而且还会导致体重平衡失调的疾病。根据这一观点，在 AD 的早期和晚期都可能会出现体重控制紊乱，同时伴随着血清瘦素含量的变化、瘦素穿过血脑屏障（BBB）的转运改变以及瘦素受体相关信号异常。瘦素是脂肪因子家族的成员，而瘦素受体属于 I 类细胞因子受体。由于细胞对脂肪因子信号的反应可以由于特定的配体-受体相互作用而增强或减弱，因此需要进一步研究瘦素与脂肪因子家族的其他成员（包括胰岛素、胃饥饿素和激素如催乳素）的相互作用。在这篇综述中，我们提供了瘦素在大脑中的功能的一般观点，特别关注散发性 AD。
