Waldmeier Peter C, Tatton William G
WKL-125.607, Neuroscience Research, Novartis Institutes for Biomedical Research (NIBR), CH-4002 Basel, Switzerland.
Drug Discov Today. 2004 Mar 1;9(5):210-8. doi: 10.1016/S1359-6446(03)03000-9.
Current treatment options for neurodegenerative diseases are limited and mainly affect only the symptoms of disease. Because of the unknown and probably multiple causes of these diseases, they cannot be readily targeted. However, it has been established that apoptosis contributes to neuronal loss in most neurodegenerative diseases. A possible treatment option is to interrupt the signaling networks that link neuronal damage to apoptotic degradation in neurodegeneration. The viability of this option depends upon the extent to which apoptosis accounts for neuron loss, whether or not interruption of apoptosis signaling results in recovery of neurological function and whether or not there are significant downsides to targeting apoptosis. Several compounds acting at different sites in known apoptotic signaling networks are currently in development and a few are in clinical trial. If an apoptosis-targeted compound succeeds in slowing or halting neurological dysfunction in one or more neurodegenerative diseases, a new era in the treatment of neurodegenerative diseases will begin.
目前神经退行性疾病的治疗选择有限,且主要仅能缓解疾病症状。由于这些疾病的病因不明且可能是多因素的,因此难以直接针对病因进行治疗。然而,已经确定细胞凋亡在大多数神经退行性疾病中导致神经元丢失。一种可能的治疗选择是中断在神经退行性变中将神经元损伤与凋亡性降解联系起来的信号网络。这种选择的可行性取决于细胞凋亡导致神经元丢失的程度、中断凋亡信号是否能恢复神经功能,以及靶向细胞凋亡是否存在重大弊端。目前有几种作用于已知凋亡信号网络不同位点的化合物正在研发中,还有一些正在进行临床试验。如果一种靶向细胞凋亡的化合物成功减缓或阻止一种或多种神经退行性疾病中的神经功能障碍,神经退行性疾病治疗的新时代将开启。