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1

Is GDNF beneficial in Parkinson disease?胶质细胞源性神经营养因子（GDNF）对帕金森病有益吗？

Nat Rev Neurol. 2011 Sep 20;7(11):600-2. doi: 10.1038/nrneurol.2011.149.

2

Histological effects of intraputaminal infusion of glial cell line-derived neurotrophic factor in Parkinson disease model macaque monkeys.在帕金森病模型猕猴中脑内注射胶质细胞源性神经营养因子的组织学效应

Neurol Med Chir (Tokyo). 2006 Jun;46(6):267-75; discussion 275-6. doi: 10.2176/nmc.46.267.

3

Intrastriatal injection of an adenoviral vector expressing glial-cell-line-derived neurotrophic factor prevents dopaminergic neuron degeneration and behavioral impairment in a rat model of Parkinson disease.在帕金森病大鼠模型中，向纹状体内注射表达胶质细胞源性神经营养因子的腺病毒载体可预防多巴胺能神经元变性和行为障碍。

Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8818-23. doi: 10.1073/pnas.94.16.8818.

4

Reviving: restoring depression-like behaviour through glial cell-derived neurotrophic factor treatment in the medial prefrontal cortex.通过胶质细胞源性神经营养因子治疗内侧前额叶皮层恢复抑郁样行为。

J Psychiatry Neurosci. 2024 Feb 1;49(1):E23-E34. doi: 10.1503/jpn.230079. Print 2024 Jan-Feb.

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[Therapeutic effect of GDNF gene-modified mesencephalic neural stem cell transplantation in a rat model of Parkinson disease].[胶质细胞源性神经营养因子基因修饰的中脑神经干细胞移植对帕金森病大鼠模型的治疗作用]

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Towards a neuroprotective gene therapy for Parkinson's disease: use of adenovirus, AAV and lentivirus vectors for gene transfer of GDNF to the nigrostriatal system in the rat Parkinson model.迈向帕金森病的神经保护基因治疗：在大鼠帕金森模型中使用腺病毒、腺相关病毒和慢病毒载体将胶质细胞源性神经营养因子基因转移至黑质纹状体系统

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Using Extracellular Vesicles Released by GDNF-Transfected Macrophages for Therapy of Parkinson Disease.使用 GDNF 转染巨噬细胞释放的细胞外囊泡治疗帕金森病。

Cells. 2022 Jun 15;11(12):1933. doi: 10.3390/cells11121933.

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GDNF-Ret signaling in midbrain dopaminergic neurons and its implication for Parkinson disease.中脑多巴胺能神经元中的胶质细胞源性神经营养因子-受体酪氨酸激酶信号传导及其与帕金森病的关联

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9

Ret is essential to mediate GDNF's neuroprotective and neuroregenerative effect in a Parkinson disease mouse model.在帕金森病小鼠模型中，Ret对于介导胶质细胞源性神经营养因子（GDNF）的神经保护和神经再生作用至关重要。

Cell Death Dis. 2016 Sep 8;7(9):e2359. doi: 10.1038/cddis.2016.263.

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Early transplantation of an encapsulated glial cell line-derived neurotrophic factor-producing cell demonstrating strong neuroprotective effects in a rat model of Parkinson disease.在帕金森病大鼠模型中显示出强大神经保护作用的封装型胶质细胞源性神经营养因子产生细胞的早期移植。

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Glial Cell Line-Derived Neurotrophic Factor Gene Delivery in Parkinson's Disease: A Delicate Balance between Neuroprotection, Trophic Effects, and Unwanted Compensatory Mechanisms.胶质细胞源性神经营养因子基因递送治疗帕金森病：神经保护、营养作用与不良代偿机制之间的微妙平衡

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2

Ret is essential to mediate GDNF's neuroprotective and neuroregenerative effect in a Parkinson disease mouse model.在帕金森病小鼠模型中，Ret对于介导胶质细胞源性神经营养因子（GDNF）的神经保护和神经再生作用至关重要。

Cell Death Dis. 2016 Sep 8;7(9):e2359. doi: 10.1038/cddis.2016.263.

3

RET revisited: expanding the oncogenic portfolio.RET 再探：扩展致癌基因谱。

Nat Rev Cancer. 2014 Mar;14(3):173-86. doi: 10.1038/nrc3680.

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The proform of glia cell line-derived neurotrophic factor: a potentially biologically active protein.胶质细胞源性神经营养因子的前体形式：一种具有潜在生物活性的蛋白质。

Mol Neurobiol. 2014 Feb;49(1):234-50. doi: 10.1007/s12035-013-8515-6. Epub 2013 Aug 10.

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Functional neuroprotection and efficient regulation of GDNF using destabilizing domains in a rodent model of Parkinson's disease.使用不稳定结构域在帕金森病的啮齿动物模型中实现功能性神经保护和 GDNF 的有效调控。

Mol Ther. 2013 Dec;21(12):2169-80. doi: 10.1038/mt.2013.169. Epub 2013 Jul 24.

6

Castration induces Parkinson disease pathologies in young male mice via inducible nitric-oxide synthase.去势通过诱导型一氧化氮合酶诱导年轻雄性小鼠发生帕金森病病变。

J Biol Chem. 2013 Jul 19;288(29):20843-20855. doi: 10.1074/jbc.M112.443556. Epub 2013 Jun 6.

7

Molecular mechanisms of RET receptor-mediated oncogenesis in multiple endocrine neoplasia 2.RET 受体介导的多发性内分泌肿瘤 2 中的致癌作用的分子机制。

Clinics (Sao Paulo). 2012;67 Suppl 1(Suppl 1):77-84. doi: 10.6061/clinics/2012(sup01)14.

本文引用的文献

1

GDNF fails to exert neuroprotection in a rat α-synuclein model of Parkinson's disease.GDNF 未能在帕金森病的大鼠 α-突触核蛋白模型中发挥神经保护作用。

Brain. 2011 Aug;134(Pt 8):2302-11. doi: 10.1093/brain/awr149. Epub 2011 Jun 28.

2

Induction of the unfolded protein response by α-synuclein in experimental models of Parkinson's disease.α-突触核蛋白在帕金森病实验模型中诱导未折叠蛋白反应。

J Neurochem. 2011 Feb;116(4):588-605. doi: 10.1111/j.1471-4159.2010.07143.x. Epub 2011 Jan 19.

3

Functional effects of AAV2-GDNF on the dopaminergic nigrostriatal pathway in parkinsonian rhesus monkeys.AAV2-GDNF 对帕金森病恒河猴多巴胺能黑质纹状体通路的功能影响。

Hum Gene Ther. 2009 May;20(5):511-8. doi: 10.1089/hum.2008.201.

4

Gene expression patterns for GDNF and its receptors in the human putamen affected by Parkinson's disease: a real-time PCR study.帕金森病影响下的人壳核中胶质细胞源性神经营养因子（GDNF）及其受体的基因表达模式：一项实时聚合酶链反应研究

Mol Cell Endocrinol. 2006 Jun 27;252(1-2):160-6. doi: 10.1016/j.mce.2006.03.013. Epub 2006 Apr 27.

5

Randomized controlled trial of intraputamenal glial cell line-derived neurotrophic factor infusion in Parkinson disease.帕金森病中脑内注射胶质细胞源性神经营养因子的随机对照试验。

Ann Neurol. 2006 Mar;59(3):459-66. doi: 10.1002/ana.20737.

6

Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease.帕金森病中经脑直接注入胶质细胞源性神经营养因子

Nat Med. 2003 May;9(5):589-95. doi: 10.1038/nm850. Epub 2003 Mar 31.

7

Clinicopathological findings following intraventricular glial-derived neurotrophic factor treatment in a patient with Parkinson's disease.帕金森病患者脑室内注射胶质细胞源性神经营养因子后的临床病理结果

Ann Neurol. 1999 Sep;46(3):419-24. doi: 10.1002/1531-8249(199909)46:3<419::aid-ana21>3.0.co;2-q.

8

Expression of the proto-oncogene Ret, a component of the GDNF receptor complex, persists in human substantia nigra neurons in Parkinson's disease.原癌基因Ret是胶质细胞源性神经营养因子（GDNF）受体复合物的一个组成部分，其表达在帕金森病患者的黑质神经元中持续存在。

Brain Res. 1998 May 11;792(2):207-17. doi: 10.1016/s0006-8993(98)00131-0.

9

Peripheral expression and biological activities of GDNF, a new neurotrophic factor for avian and mammalian peripheral neurons.胶质细胞源性神经营养因子（GDNF）在外周的表达及生物学活性，GDNF是一种针对鸟类和哺乳动物外周神经元的新型神经营养因子。

J Cell Biol. 1995 Jul;130(1):137-48. doi: 10.1083/jcb.130.1.137.

10

Glial cell line-derived neurotrophic factor augments midbrain dopaminergic circuits in vivo.胶质细胞系源性神经营养因子增强体内中脑多巴胺能神经回路。

Brain Res Bull. 1995;36(5):425-32. doi: 10.1016/0361-9230(94)00224-o.

胶质细胞源性神经营养因子（GDNF）对帕金森病有益吗？

Is GDNF beneficial in Parkinson disease?

出版信息

Nat Rev Neurol. 2011 Sep 20;7(11):600-2. doi: 10.1038/nrneurol.2011.149.

DOI:10.1038/nrneurol.2011.149

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3830920/

Abstract

Glial cell line-derived neurotrophic factor (GDNF) has proved efficacious in treatment of neurodegeneration in toxin-induced models of Parkinson disease (PD), but clinical trials have been equivocal. Do the results of a recent study—suggesting that GDNF is ineffective in an α-synuclein-overexpression PD model—exclude GDNF as a therapy for PD?

摘要

胶质细胞源性神经营养因子（GDNF）已被证明在治疗帕金森病（PD）的毒素诱导模型中的神经退行性变方面是有效的，但临床试验结果却存在争议。最近的一项研究结果表明，GDNF 在α-突触核蛋白过表达 PD 模型中无效，这是否排除了 GDNF 作为 PD 治疗方法的可能性？