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克氏锥虫源性神经营养因子:在神经修复和神经保护中的作用

Trypanosoma cruzi-Derived Neurotrophic Factor: Role in Neural Repair and Neuroprotection.

作者信息

Chuenkova Marina V, Pereiraperrin Mercio

机构信息

Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111, USA.

出版信息

J Neuroparasitology. 2010 Jul 26;1:55-60. doi: 10.4303/jnp/N100507.

Abstract

Some patients infected with the parasite Try-panosoma cruzi develop chronic Chagas' disease, while others remain asymptomatic for life. Although pathological mechanisms that govern disease progression remain unclear, the balance between degeneration and regeneration in the peripheral nervous system seems to contribute to the different clinical outcomes. This review focuses on certain new aspects of host-parasite interactions related to regeneration in the host nervous system induced by the trans-sialidase of T. cruzi, also known as a parasite-derived neurotrophic factor (PDNF). PDNF plays multiple roles in T. cruzi infection, ranging from immunosuppression to functional mimicry of mammalian neurotrophic factors and inhibition of apoptosis. PDNF affinity to neurotrophin Trk receptors provide sustained activation of cellular survival mechanisms resulting in neuroprotection and neuronal repair, resistance to cytotoxic insults and enhancement of neuritogenesis. Such unique PDNF-elicited regenerative responses likely prolong parasite persistence in infected tissues while reducing neuropathology in Chagas' disease.

摘要

一些感染克氏锥虫寄生虫的患者会发展为慢性恰加斯病,而其他患者则终生无症状。尽管疾病进展的病理机制尚不清楚,但外周神经系统中变性与再生之间的平衡似乎导致了不同的临床结果。本综述聚焦于宿主-寄生虫相互作用的某些新方面,这些方面与克氏锥虫转唾液酸酶(也称为寄生虫衍生神经营养因子,PDNF)诱导的宿主神经系统再生有关。PDNF在克氏锥虫感染中发挥多种作用,从免疫抑制到模拟哺乳动物神经营养因子的功能以及抑制细胞凋亡。PDNF与神经营养因子Trk受体的亲和力可提供细胞存活机制的持续激活,从而实现神经保护和神经元修复、抵抗细胞毒性损伤并增强神经突生成。这种独特的PDNF引发的再生反应可能会延长寄生虫在感染组织中的持续存在,同时减少恰加斯病中的神经病理学。

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Chagas disease.恰加斯病。
Lancet. 2010 Apr 17;375(9723):1388-402. doi: 10.1016/S0140-6736(10)60061-X.
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The chronic gastrointestinal manifestations of Chagas disease.恰加斯病的慢性胃肠道表现。
Clinics (Sao Paulo). 2009;64(12):1219-24. doi: 10.1590/S1807-59322009001200013.
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Fighting the oxidative assault: the Trypanosoma cruzi journey to infection.对抗氧化攻击:克氏锥虫的感染之旅
Curr Opin Microbiol. 2009 Aug;12(4):415-21. doi: 10.1016/j.mib.2009.06.011. Epub 2009 Jul 17.

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