Department of Cellular and Molecular Medicine and Department of Neurosciences, UCSD School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0695, USA.
Prog Neurobiol. 2012 Dec;99(3):186-90. doi: 10.1016/j.pneurobio.2012.03.006. Epub 2012 Apr 1.
Although it is well established that axonal transport defects are part of the initiation or progression of some neurodegenerative diseases, the precise role of these defects in disease development is poorly understood. Thus, in this article, rather than enumerate the already well-reviewed evidence that there are transport deficits in disease, I will focus on a discussion of two crucial and unanswered questions about the possible role of axonal transport defects in HD and AD. (1) Are alterations in axonal transport caused by changes in the normal function of proteins mutated or altered in HD and AD and/or do such alterations in transport occur as a result of the formation of toxic aggregates of peptides or proteins? (2) Do alterations in axonal transport contribute to the causes of HD and AD or are they early, or late, secondary consequences of other cellular defects caused by disease-induction?
虽然轴突运输缺陷是一些神经退行性疾病发生或进展的一部分这一事实已得到充分证实，但这些缺陷在疾病发展中的确切作用仍知之甚少。因此，在本文中，我将不会列举已经被充分审查过的证据，即疾病存在运输缺陷，而是将重点讨论关于在 HD 和 AD 中轴突运输缺陷可能作用的两个关键且尚未解答的问题。（1）HD 和 AD 中突变或改变的蛋白质的正常功能变化引起的轴突运输改变，还是由于肽或蛋白质的毒性聚集的形成而发生这种运输改变？（2）轴突运输的改变是否导致 HD 和 AD 的发生，还是疾病诱导引起的其他细胞缺陷的早期或晚期继发后果？
