Glial cell line-derived neurotrophic factor family ligands and their therapeutic potential

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• 作者：Y. A. Sidorova ; M. Saarma
• 刊名：Molecular Biology
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：50
• 期：4
• 页码：521-531
• 全文大小：827 KB
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Life Sciences
  Biochemistry
  Human Genetics
  Russian Library of Science
  
• 出版者：MAIK Nauka/Interperiodica distributed exclusively by Springer Science+Business Media LLC.
• ISSN：1608-3245
• 卷排序：50

文摘

Four glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) have been characterized: GDNF, neurturin (NRTN), artemin (ARTN) and persephin (PSPN). These proteins support and restore multiple neuronal populations such as dopaminergic, sensory, motor, hippocampal, basal forebrain, enteric, sympathetic and parasympathetic neurons. Therefore, GFLs attracted significant attention as a potential cure for the diseases caused by neuronal injury and degeneration. Results of multiple experiments indicate that GFLs can alleviate behavioral symptoms and restore affected neurons in animal models of several neurological disorders including, among others, Parkinson’s disease (PD). During the last decade, GDNF protein and NRTN gene therapy have been tested in several clinical trials in patients with PD. Although the results of phase I clinical trials were positive, phase II clinical trials failed to reach primary end-points. Poor pharmacokinetic properties of GFLs (inability to penetrate tissues barriers, high affinity for extracellular matrix, etc.) could contribute to the absence of clear clinical benefits of these proteins for the patients. The purpose of this paper was to review therapeutic potential of GFLs and discuss possibilities to overcome difficulties associated with pharmacokinetic properties and delivery of GFLs to target neurons.Keywordsglial cell line-derived neurotrophic factor (GDNF)GDNF family ligands (GFLs)GDNF family receptor α (GFRα)RET receptor tyrosine kinaseartemin (ARTN)neurturin (NRTN)persephin (PSPN)small molecular weight GFL mimeticsParkinson’s diseaseneuropathic pain