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瘦素对神经疾病中胶质细胞的影响。

The Effects of Leptin on Glial Cells in Neurological Diseases.

作者信息

Fujita Yuki, Yamashita Toshihide

机构信息

Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Osaka, Japan.

WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.

出版信息

Front Neurosci. 2019 Aug 7;13:828. doi: 10.3389/fnins.2019.00828. eCollection 2019.

Abstract

It is known that various endocrine modulators, including leptin and ghrelin, have neuroprotective roles in neurological diseases. Leptin is a hormone produced by adipocytes and was originally identified as a gene related to obesity in mice. The leptin receptors in the hypothalamus are the main target for the homeostatic regulation of body weight. Recent studies have demonstrated that leptin receptors are also expressed in other regions of the central nervous system (CNS), such as the hippocampus, cerebral cortex, and spinal cord. Accordingly, these studies identified the involvement of leptin in the regulation of neuronal survival and neural development. Furthermore, leptin has been shown to have neuroprotective functions in animal models of neurological diseases and demyelination. These observations also suggest that dysregulation of leptin signaling may be involved in the association between neurodegeneration and obesity. In this review, we summarize novel functions of leptin in animal models of neurodegenerative diseases. Specifically, we focus on the emerging evidence for the role of leptin in non-neuronal cells in the CNS, including astrocytes, microglia, and oligodendrocytes. Understanding leptin-mediated neuroprotective signals and molecular mechanisms underlying remyelination will be helpful to establish therapeutic strategies against neurological diseases.

摘要

众所周知,包括瘦素和胃饥饿素在内的各种内分泌调节剂在神经疾病中具有神经保护作用。瘦素是一种由脂肪细胞产生的激素,最初被鉴定为与小鼠肥胖相关的基因。下丘脑的瘦素受体是体重稳态调节的主要靶点。最近的研究表明,瘦素受体也在中枢神经系统(CNS)的其他区域表达,如海马体、大脑皮层和脊髓。因此,这些研究确定了瘦素参与神经元存活和神经发育的调节。此外,在神经疾病和脱髓鞘的动物模型中,瘦素已被证明具有神经保护功能。这些观察结果还表明,瘦素信号失调可能与神经退行性变和肥胖之间的关联有关。在这篇综述中,我们总结了瘦素在神经退行性疾病动物模型中的新功能。具体而言,我们关注瘦素在中枢神经系统非神经元细胞(包括星形胶质细胞、小胶质细胞和少突胶质细胞)中作用的新证据。了解瘦素介导的神经保护信号和髓鞘再生的分子机制将有助于建立针对神经疾病的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17e7/6692660/d0f87625e272/fnins-13-00828-g001.jpg

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