摘要
在中枢神经系统中,星形胶质细胞是最丰富的神经元胶质细胞,星形胶质细胞的神经保护作用已在多种神经系统疾病如肌萎缩性侧索硬化,脊髓损伤,中风和帕金森病(PD)中被证明了。星形胶质细胞功能障碍或损失增加了神经元细胞死亡的敏感性,而在动物研究中,有移植治疗的优势。我们最近有报道,5-羟色胺1A(5-HT1A)受体对星形胶质细胞的刺激促进了增殖以及上调了帕金森小鼠的神经保护作用受体的抗氧化分子。PD是一种渐进性的神经退行性疾病,有运动症状如震颤、运动迟缓、僵直和姿势不稳,这是由于黑质纹状体多巴胺能神经元选择性的损失,基于外周神经退行性病的基础,产生非运动症状如体位性低血压和便秘等。虽然管理与帕金森病相关的运动残疾的多巴胺治疗目前仍在评估中,但当前最大的挑战依然是神经保护和疾病修饰的治疗发展情况。因此,人们希望找到治疗方法来延缓多巴胺细胞的死亡进程。在这篇文章中,我们总结了星形胶质细胞与帕金森病第一相关的特定分子的神经保护物质,接着,我们回顾了星形胶质细胞中由5-羟色胺受体刺激产生的神经保护作用。这篇综述讨论了在针对氧化应激的神经保护作用和预防多巴胺能神经元变性的基础上,新的有前景的治疗策略。
关键词: 5-HT1A受体;S100β;星形胶质细胞;帕金森病;神经保护;多巴胺能神经元。
Current Medicinal Chemistry
Title:Serotonin 1A Receptors on Astrocytes as a Potential Target for the Treatment of Parkinson’s Disease
Volume: 23 Issue: 7
Author(s): Ikuko Miyazaki and Masato Asanuma
Affiliation:
关键词: 5-HT1A受体;S100β;星形胶质细胞;帕金森病;神经保护;多巴胺能神经元。
摘要: Astrocytes are the most abundant neuron-supporting glial cells in the central nervous system. The neuroprotective role of astrocytes has been demonstrated in various neurological disorders such as amyotrophic lateral sclerosis, spinal cord injury, stroke and Parkinson’s disease (PD). Astrocyte dysfunction or loss-of-astrocytes increases the susceptibility of neurons to cell death, while astrocyte transplantation in animal studies has therapeutic advantage. We reported recently that stimulation of serotonin 1A (5-HT1A) receptors on astrocytes promoted astrocyte proliferation and upregulated antioxidative molecules to act as a neuroprotectant in parkinsonian mice. PD is a progressive neurodegenerative disease with motor symptoms such as tremor, bradykinesia, rigidity and postural instability, that are based on selective loss of nigrostriatal dopaminergic neurons, and with non-motor symptoms such as orthostatic hypotension and constipation based on peripheral neurodegeneration. Although dopaminergic therapy for managing the motor disability associated with PD is being assessed at present, the main challenge remains the development of neuroprotective or disease- modifying treatments. Therefore, it is desirable to find treatments that can reduce the progression of dopaminergic cell death. In this article, we summarize first the neuroprotective properties of astrocytes targeting certain molecules related to PD. Next, we review neuroprotective effects induced by stimulation of 5-HT1A receptors on astrocytes. The review discusses new promising therapeutic strategies based on neuroprotection against oxidative stress and prevention of dopaminergic neurodegeneration.
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Ikuko Miyazaki and Masato Asanuma , Serotonin 1A Receptors on Astrocytes as a Potential Target for the Treatment of Parkinson’s Disease, Current Medicinal Chemistry 2016; 23 (7) . https://dx.doi.org/10.2174/0929867323666160122115057
DOI https://dx.doi.org/10.2174/0929867323666160122115057 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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