Dorothy Hodgkin Building, Whitson St, Bristol BS1 3NY, UK.
Pharmacol Ther. 2013 May;138(2):155-75. doi: 10.1016/j.pharmthera.2013.01.004. Epub 2013 Jan 21.
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.
胶质细胞源性神经营养因子 (GDNF) 以及神经营养因子神经生长因子 (NGF) 和脑源性神经营养因子 (BDNF) 对于成年大脑中特定神经元群体的存活、维持和再生非常重要。这些神经营养因子的耗竭与疾病的病理和症状有关，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。最近的研究表明，GDNF 给药是治疗帕金森病的有效方法，目前正在进行临床试验。针对阿尔茨海默病的 NGF 试验正在进行中，取得了一定程度的成功。使用 BDNF 的临床前研究结果也显示出很大的希望，尽管存在一些困难。最终，在大脑中使用蛋白质治疗存在固有问题。由于血脑屏障的存在，蛋白质必须直接输注、通过病毒构建体产生、从植入的蛋白质分泌细胞中分泌或主动跨脑转运。一种替代方法是使用小分子激动剂、针对相关受体的调节剂或增强剂。我们将这些神经营养因子评估为潜在的短期或长期治疗方法，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。
