Cañete-Soler Rafaela, Schlaepfer William W
Division of Neuropathology, University of Pennsylvania Medical School, Philadelphia, PA 19104, USA.
Ann Neurol. 2007 Jul;62(1):8-14. doi: 10.1002/ana.21128.
The success in mapping genetic loci and identifying mutant genes in familial neurodegenerative disease has outpaced our ability to understand the linkage between genotype and phenotype of disease. The results have led to a backlog of genetic information with limited clarification of underlying disease mechanisms. A major dilemma is how mutations in widely expressed proteins lead to degeneration or dysfunction of small subsets of neurons. The problem raises fundamental questions as to the nature and interrelation of pathways that maintain the homeostasis of differentiated neurons. The issue also bears on the pathogenesis of sporadic forms of disease and prospective efficacy of therapeutic applications. This review examines the problem as it relates to motor neuron disease.
在绘制家族性神经退行性疾病的基因位点图谱和鉴定突变基因方面所取得的成功，已经超过了我们理解疾病基因型与表型之间联系的能力。这些结果导致了遗传信息的积压，而对潜在疾病机制的阐释却很有限。一个主要困境是，广泛表达的蛋白质中的突变如何导致一小部分神经元的退化或功能障碍。这个问题引发了关于维持分化神经元内稳态的途径的性质和相互关系的基本问题。该问题也与散发性疾病的发病机制及治疗应用的预期疗效相关。本综述探讨了与运动神经元病相关的这一问题。
