De Yébenes Justo Garcia, Sánchez Marina, Mena Maria Angeles
Servicio de Neurología, Fundación Jiménez Díaz, Av. Reyes Católicos 2, Madrid 28040, Spain.
Neurotox Res. 2003;5(1-2):119-38. doi: 10.1007/BF03033377.
Neurotrophic factors (NFs) are proteins that enhance neuronal survival, differentiation, neurotransmitter function and resistance to neurotoxins and lesions. For these reasons the NFs are considered as a new potential therapeutic tool for the treatment of neurodegenerative disorders, a group of diseases that produce the most important cause for disability in the Western world. Some NFs prevent or even reverse the behavioral, biochemical, pharmacological and histological abnormalities observed in several in vitro and in vivo models of neurodegenerative disorders, namely Parkinson's disease. Several NFs have been investigated in primate models of neurological disorders and some of them have been used for patients with these diseases. The results so far obtained in humans have been disappointing for several reasons, including technical problems for delivery, unbearable side effects or lack of efficacy. Future approaches for the use of NFs in humans should include the following: (1) Investigation of the putative compounds in animal models more related to the pathophysiology of each disease, such as in genetic models of neurodegenerative diseases; (2) New methods of delivery including genetic engineering by viral vectors and administration through implantable devices; (3) More precise methods of continuous response evaluation, including the novel neuroimaging techniques; (4) Investigation of the effects of behavioral stimulation and conventional pharmacotherapy on the metabolism of NFs.
神经营养因子（NFs）是一类蛋白质，可增强神经元的存活、分化、神经递质功能以及对神经毒素和损伤的抵抗力。基于这些原因，NFs被视为治疗神经退行性疾病的一种新的潜在治疗工具，神经退行性疾病是导致西方世界残疾的最重要原因之一。一些NFs可预防甚至逆转在神经退行性疾病（如帕金森病）的多种体外和体内模型中观察到的行为、生化、药理和组织学异常。几种NFs已在神经疾病的灵长类动物模型中进行了研究，其中一些已用于患有这些疾病的患者。迄今为止，在人类身上获得的结果令人失望，原因有几个，包括给药的技术问题、无法忍受的副作用或缺乏疗效。未来在人类中使用NFs的方法应包括以下几点：（1）在与每种疾病的病理生理学更相关的动物模型中研究推定的化合物，如在神经退行性疾病的遗传模型中；（2）新的给药方法，包括通过病毒载体进行基因工程和通过可植入装置给药；（3）更精确的连续反应评估方法，包括新型神经成像技术；（4）研究行为刺激和传统药物治疗对NFs代谢的影响。
