Houck Alexander L, Seddighi Sahba, Driver Jane A
College of Medicine, University of Tennessee Health Science Center, Memphis, TN, United States.
Clinical and Translational Neuroscience Unit, Laboratory of Behavioral Neuroscience, National Institute on Aging (NIA), National Institutes of Health (NIH), Baltimore, MD, United States.
Curr Aging Sci. 2018;11(2):77-89. doi: 10.2174/1874609811666180223154436.
A growing body of epidemiologic evidence suggests that neurodegenerative diseases occur less frequently in cancer survivors, and vice versa. While unusual, this inverse comorbidity is biologically plausible and could be explained, in part, by the evolutionary tradeoffs made by neurons and cycling cells to optimize the performance of their very different functions. The two cell types utilize the same proteins and pathways in different, and sometimes opposite, ways. However, cancer and neurodegeneration also share many pathophysiological features.
In this review, we compare three overlapping aspects of neurodegeneration and cancer.
First, we contrast the priorities and tradeoffs of dividing cells and neurons and how these manifest in disease. Second, we consider the hallmarks of biological aging that underlie both neurodegeneration and cancer. Finally, we utilize information from genetic databases to outline specific genes and pathways common to both diseases.
We argue that a detailed understanding of the biologic and genetic relationships between cancer and neurodegeneration can guide future efforts in designing disease-modifying therapeutic interventions. Lastly, strategies that target aging may prevent or delay both conditions.
越来越多的流行病学证据表明,神经退行性疾病在癌症幸存者中发病率较低,反之亦然。虽然这种反向共病现象并不常见,但从生物学角度来看是合理的,部分原因可能是神经元和循环细胞为优化其截然不同的功能而进行的进化权衡。这两种细胞类型以不同的、有时甚至相反的方式利用相同的蛋白质和信号通路。然而,癌症和神经退行性疾病也有许多共同的病理生理特征。
在本综述中,我们比较神经退行性疾病和癌症三个重叠的方面。
首先,我们对比分裂细胞和神经元的优先事项与权衡,以及这些如何在疾病中表现出来。其次,我们考虑神经退行性疾病和癌症共同的生物衰老特征。最后,我们利用基因数据库中的信息概述这两种疾病共有的特定基因和信号通路。
我们认为,详细了解癌症与神经退行性疾病之间的生物学和遗传关系可以指导未来设计疾病修饰治疗干预措施的努力。最后,针对衰老的策略可能预防或延缓这两种疾病。