Tuszynski Mark H
Department of Neurosciences-0626, University of California-San Diego, La Jolla, California 92093, USA.
Dev Neurobiol. 2007 Aug;67(9):1204-15. doi: 10.1002/dneu.20510.
Cell death is the final common pathway of cognitive decline in Alzheimer's disease (AD). Nervous system growth factors, or neurotrophic factors, are substances naturally produced in the nervous system that support neuronal survival during development and influence neuronal function throughout adulthood. Notably, in animal models, including primates, neurotrophic factors prevent neuronal death after injury and can reverse spontaneous neuronal atrophy in aging. Thus, neurotrophic factor therapy has the potential to prevent or reduce ongoing cell loss in disorders such as AD. The main challenge in clinical testing of neurotrophic factors has been their delivery to the brain in sufficient doses to impact cell function, while restricting their delivery to specific sites to prevent adverse effects from broad distribution. This article reviews progress in evaluating the therapeutic potential of growth factors, from early animal models to human clinical trials currently underway in AD.
细胞死亡是阿尔茨海默病（AD）认知衰退的最终共同途径。神经系统生长因子，即神经营养因子，是神经系统自然产生的物质，在发育过程中支持神经元存活，并在成年期影响神经元功能。值得注意的是，在包括灵长类动物在内的动物模型中，神经营养因子可防止损伤后神经元死亡，并能逆转衰老过程中自发的神经元萎缩。因此，神经营养因子疗法有可能预防或减少AD等疾病中持续的细胞丢失。神经营养因子临床试验的主要挑战在于，要以足够的剂量将其输送到大脑以影响细胞功能，同时将其输送限制在特定部位，以防止广泛分布带来的不良反应。本文综述了从早期动物模型到目前正在进行的AD人类临床试验中评估生长因子治疗潜力的进展。
