Seeburger J L, Springer J E
Department of Neurology, Hahnemann University, Philadelphia, Pennsylvania 19102-1192.
Exp Neurol. 1993 Nov;124(1):64-72. doi: 10.1006/exnr.1993.1176.
Current therapeutic efforts to treat chronic and progressive neurodegenerative disease include, for the first time, attempts to regenerate affected nervous tissue using neurotrophic factors. The rationale for using trophic factors includes the understanding that they support neuronal survival and regrowth processes. The potential benefits of trophic factor therapy will be no more realized in the near future than in the treatment of amyotrophic lateral sclerosis (ALS). ALS is pathologically characterized by the selective degeneration of specific populations of cranial and spinal motoneurons. Evidence for the existence of factors that support motoneurons has come from studies demonstrating that motoneurons receive trophic influences from various tissues, both central and peripheral, within their local environment. Although the identity of these putative tissue-derived factors has remained enigmatic, recent studies have demonstrated that several previously characterized trophic factors exhibit trophic influences on motoneurons. Among these are several members of the neurotrophin family, most notably brain-derived neurotrophic factor. These neurotrophins meet most of the criteria to be considered motoneuron trophic factors: they are locally available to motoneurons in vivo; motoneurons express specific receptors for these factors; and exogenous application of these factors mimicks the effects of the uncharacterized endogenous agents. The clinical use of these factors for the treatment of ALS, therefore, appears to be scientifically justified.
目前，针对慢性进行性神经退行性疾病的治疗努力首次包括尝试使用神经营养因子来再生受影响的神经组织。使用营养因子的基本原理包括认识到它们支持神经元的存活和再生过程。营养因子疗法的潜在益处近期内不会比在肌萎缩侧索硬化症（ALS）的治疗中更易实现。ALS的病理特征是特定的颅神经和脊髓运动神经元群体选择性退化。支持运动神经元的因子存在的证据来自多项研究，这些研究表明运动神经元在其局部环境中受到来自中枢和外周各种组织的营养影响。尽管这些假定的组织衍生因子的身份仍然不明，但最近的研究表明，几种先前已被表征的营养因子对运动神经元表现出营养影响。其中包括神经营养因子家族的几个成员，最显著的是脑源性神经营养因子。这些神经营养因子符合被视为运动神经元营养因子的大多数标准：它们在体内可被运动神经元局部获取；运动神经元表达这些因子的特异性受体；并且这些因子的外源性应用模拟了未表征的内源性因子的作用。因此，这些因子用于治疗ALS的临床应用在科学上似乎是合理的。
