Roy Subhojit, Zhang Bin, Lee Virginia M-Y, Trojanowski John Q
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, 19104-4283, USA.
Acta Neuropathol. 2005 Jan;109(1):5-13. doi: 10.1007/s00401-004-0952-x. Epub 2005 Jan 12.
A core pathology central to most neurodegenerative diseases is the misfolding, fibrillization and aggregation of disease proteins to form the hallmark lesions of specific disorders. The mechanisms underlying these brain-specific neurodegenerative amyloidoses are the focus of intense investigation and defective axonal transport has been hypothesized to play a mechanistic role in several neurodegenerative disorders; however, this hypothesis has not been extensively examined. Discoveries of mutations in human genes encoding motor proteins responsible for axonal transport do provide direct evidence for the involvement of axonal transport in neurodegenerative diseases, and this evidence is supported by studies of animal models of neurodegeneration. In this review, we summarize recent findings related to axonal transport and neurodegeneration. Focusing on specific neurodegenerative diseases from a neuropathologic perspective, we highlight discoveries of human motor protein mutations in some of these diseases, as well as illustrate new insights from animal models of neurodegenerative disorders. We also review the current understanding of the biology of axonal transport including major recent findings related to slow axonal transport.
大多数神经退行性疾病的核心病理学特征是疾病相关蛋白发生错误折叠、纤维化和聚集，从而形成特定疾病的标志性病变。这些脑部特异性神经退行性淀粉样变的潜在机制是深入研究的重点，轴突运输缺陷被认为在几种神经退行性疾病中起作用；然而，这一假说尚未得到广泛验证。编码负责轴突运输的运动蛋白的人类基因突变的发现确实为轴突运输参与神经退行性疾病提供了直接证据，神经退行性疾病动物模型的研究也支持了这一证据。在本综述中，我们总结了与轴突运输和神经退行性变相关的最新研究结果。从神经病理学角度关注特定的神经退行性疾病，我们强调了在其中一些疾病中人类运动蛋白突变的发现，并阐述了神经退行性疾病动物模型的新见解。我们还回顾了目前对轴突运输生物学的理解，包括与慢速轴突运输相关的主要最新研究结果。
