Department of Neurodegenerative Disease, University College London, Queen Square, London, WC1N 3BG, UK.
Mamm Genome. 2011 Apr;22(3-4):139-47. doi: 10.1007/s00335-011-9319-5. Epub 2011 Mar 4.
Through many different routes of analysis, including human familial studies and animal models, we are identifying an increasing number of genes that are causative for human neurodegenerative disease and are now in a position for many such disorders to dissect the molecular pathology that gives rise to neuronal death. Yet a paradox remains: The majority of the genes identified cause neurodegeneration in specific neuronal subtypes, but the genes themselves are ubiquitously expressed. Furthermore, the different mutations in the same gene may cause quite different types of neurodegeneration. Something in our understanding of neurodegenerative disease is clearly missing, and we refer to this as the phenomenon of "neuronal targeting." Here we discuss possible explanations for neuronal targeting, why specific neuronal subtypes are vulnerable to specific mutations in ubiquitously expressed genes.
通过多种不同的分析途径，包括人类家族研究和动物模型，我们正在确定越来越多的导致人类神经退行性疾病的基因，现在许多这样的疾病都可以剖析导致神经元死亡的分子病理学。然而，一个悖论仍然存在：大多数确定的基因导致特定神经元亚型的神经退行性变，但这些基因本身是普遍表达的。此外，同一基因中的不同突变可能导致完全不同类型的神经退行性变。我们对神经退行性疾病的理解显然存在缺失，我们称之为“神经元靶向”现象。在这里，我们讨论了神经元靶向的可能解释，以及为什么特定的神经元亚型容易受到普遍表达的基因中特定突变的影响。
