<br>GDNF、NGF 和 BDNF 作为神经退行性疾病的治疗选择。,Pharmacology & Therapeutics

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GDNF、NGF 和 BDNF 作为神经退行性疾病的治疗选择。
Pharmacology & Therapeutics ( IF 12.0 ) Pub Date : 2013-01-26 , DOI: 10.1016/j.pharmthera.2013.01.004
Shelley J Allen ₁ , Judy J Watson , Deborah K Shoemark , Neil U Barua , Nikunj K Patel

Affiliation

胶质细胞源性神经营养因子（GDNF）、神经营养蛋白神经生长因子（NGF）和脑源性神经营养因子（BDNF）对于成人大脑中特定神经元群的生存、维持和再生非常重要。这些神经营养因子的消耗与疾病病理和症状有关，替代策略被认为是治疗帕金森病、阿尔茨海默病和亨廷顿病等神经退行性疾病的潜在疗法。最近，GDNF 给药已被证明是治疗帕金森病的有效方法，目前临床试验正在进行中。 NGF 治疗阿尔茨海默病的试验正在进行中，并取得了一定程度的成功。使用 BDNF 的临床前结果也显示出很大的希望，尽管也存在一些困难。最终，涉及大脑蛋白质的疗法的实施存在固有的问题。由于存在血脑屏障，蛋白质必须直接输注、由病毒构建体产生、由植入的蛋白质分泌细胞分泌或主动转运穿过大脑。另一种方法是使用针对相关受体的小分子激动剂、调节剂或增强剂。我们评估这些神经营养因子作为潜在的短期或长期治疗，权衡临床前和临床结果以及对潜在神经退行性过程的可能影响。

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GDNF, NGF and BDNF as therapeutic options for neurodegeneration.

Glial cell-derived neurotrophic factor (GDNF), and the neurotrophin nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are important for the survival, maintenance and regeneration of specific neuronal populations in the adult brain. Depletion of these neurotrophic factors has been linked with disease pathology and symptoms, and replacement strategies are considered as potential therapeutics for neurodegenerative diseases such as Parkinson's, Alzheimer's and Huntington's diseases. GDNF administration has recently been shown to be an effective treatment for Parkinson's disease, with clinical trials currently in progress. Trials with NGF for Alzheimer's disease are ongoing, with some degree of success. Preclinical results using BDNF also show much promise, although there are accompanying difficulties. Ultimately, the administration of a therapy involving proteins in the brain has inherent problems. Because of the blood-brain-barrier, the protein must be infused directly, produced by viral constructs, secreted from implanted protein-secreting cells or actively transported across the brain. An alternative to this is the use of a small molecule agonist, a modulator or enhancer targeting the associated receptors. We evaluate these neurotrophic factors as potential short or long-term treatments, weighing up preclinical and clinical results with the possible effects on the underlying neurodegenerative process.

更新日期：2013-01-21

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