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肿瘤坏死因子在帕金森病相关神经炎症中的作用及靶向治疗。

The role of Tumour Necrosis Factor in neuroinflammation associated with Parkinson's disease and targeted therapies.

机构信息

Faculty of Pharmaceutical Science, Assam Down Town University, Panikhaiti, Guwahati, Assam, India.

Facultad de Ciencias de la Salud, Universidad Arturo Prat, Avda. Arturo Prat 2120, Iquique, 1110939, Chile.

出版信息

Neurochem Int. 2022 Sep;158:105376. doi: 10.1016/j.neuint.2022.105376. Epub 2022 Jun 3.

Abstract

Neurodegenerative disorders Parkinson's disease is a progressive neurodegenerative disorder associated with neuroinflammatory responses that lead to the neurodegeneration of the dopaminergic neurons. These neuroinflammatory mechanisms involve various cytokines produced by the activated glial cells. Tumour Necrosis factor α (TNF α) is one of the major mediators of the neuroinflammation associated with neurodegeneration. TNF α has a dual role of neuroprotection and neurotoxicity in the brain. The effective pathways of TNF involve various signalling pathways transduced by the receptors TNFR1 and TNFR2. Effective therapeutic strategies have been produced targeting the neurotoxic behaviour of the Tumour Necrosis Factor and the associated neurodegeneration which includes the use of Dominant Negative Tumour Necrosis Factor (DN-TNF) inhibitors like XENP 345 and XPro®1595 and peroxisome proliferator receptor gamma (PPAR-γ) agonists.

摘要

神经退行性疾病帕金森病是一种与神经炎症反应相关的进行性神经退行性疾病,导致多巴胺能神经元的神经退行性变。这些神经炎症机制涉及由激活的神经胶质细胞产生的各种细胞因子。肿瘤坏死因子α(TNFα)是与神经退行性变相关的神经炎症的主要介质之一。TNFα 在大脑中具有神经保护和神经毒性的双重作用。TNF 的有效途径涉及由受体 TNFR1 和 TNFR2 转导的各种信号通路。已经产生了针对肿瘤坏死因子的神经毒性行为和相关神经退行性变的有效治疗策略,包括使用显性负性肿瘤坏死因子(DN-TNF)抑制剂,如 XENP 345 和 XPro®1595,以及过氧化物酶体增殖物激活受体γ(PPAR-γ)激动剂。

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