肾上腺素能受体作为帕金森病神经炎症和神经退行性变的药理靶点

Monika Sharma, Patrick Flood
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引用次数: 4

摘要

炎症是进展性帕金森病(PD)中多巴胺能神经变性的关键组成部分。激活的胶质细胞的存在,先天免疫系统的参与,炎症分子如细胞因子和趋化因子的增加,氧化应激和活性氧的增加是进展性PD的主要神经炎症特征。抑制胶质细胞(主要是小胶质细胞)的促炎反应的治疗靶点已被证明是减缓或消除黑质内神经元进行性变性的有效治疗方法。在本章中,我们将详细介绍一种使用β 2-肾上腺素能受体激动剂的特异性抗炎治疗,这种激动剂已被证明是多巴胺能神经变性模型的有效治疗方法,并且对进行性PD患者有效。我们还将详细介绍这种治疗在中枢神经系统内停止或逆转炎症的可能分子机制。
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Adrenergic Receptors as Pharmacological Targets for Neuroinflammation and Neurodegeneration in Parkinson’s Disease
Inflammation is a key component of the dopaminergic neurodegeneration seen in progressive Parkinson’s disease (PD). The presence of activated glial cells, the participation of innate immune system, increased inflammatory molecules such as cytokines and chemokines, and increased oxidative stress and reactive oxygen species are the main neuroinflammatory characteristics present in progressive PD. Therapeutic targets which suppress pro-inflammatory responses by glial cells (mainly microglia) have been shown to be effective treatments for slowing or eliminating the progressive degeneration of neurons within the substantia nigra. In this chapter, we will detail a specific anti-inflammatory therapy using agonists to β 2-adrenergic receptors that have been shown to be effective treatments for models of dopaminergic neurodegeneration and that have had efficacy in patients with progressive PD. We will also detail the possible molecular mechanisms of action of this therapeutic in stopping or reversing inflammation within the CNS.
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