Kwong Linda K, Uryu Kunihiro, Trojanowski John Q, Lee Virginia M-Y
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-4283, USA.
Neurosignals. 2008;16(1):41-51. doi: 10.1159/000109758. Epub 2007 Dec 5.
In this review, we summarize recent advances in understanding frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS) and related neurodegenerative disorders that are collectively known as TDP-43 proteinopathies, since transactive response DNA-binding protein 43 (TDP-43) was recently shown to be the major component of the ubiquitinated inclusions that are their pathological hallmarks. TDP-43 proteinopathies are distinct from most other neurodegenerative disorders because TDP-43 inclusions are not amyloid deposits. Besides TDP-43-positive inclusions, both sporadic and familial forms of FTLD and ALS have the pathologic TDP-43 signature of abnormal hyperphosphorylation, ubiquitination and C-terminal fragments in affected brain and spinal cord, suggesting that they share a common mechanism of pathogenesis. Thus, these findings support the concept that FTLD and ALS represent a clinicopathologic spectrum of one disease, that is, TDP-43 proteinopathy.
在本综述中，我们总结了近期在理解额颞叶痴呆（FTLD）、肌萎缩侧索硬化症（ALS）以及相关神经退行性疾病方面取得的进展，这些疾病统称为TDP-43蛋白病，因为近期研究表明，反式激活应答DNA结合蛋白43（TDP-43）是构成其病理标志——泛素化包涵体的主要成分。TDP-43蛋白病与大多数其他神经退行性疾病不同，因为TDP-43包涵体并非淀粉样沉积物。除了TDP-43阳性包涵体外，散发性和家族性的FTLD及ALS在受影响的脑和脊髓中均具有异常过度磷酸化、泛素化以及C端片段等病理性TDP-43特征，这表明它们具有共同的发病机制。因此，这些发现支持了这样一个概念，即FTLD和ALS代表了一种疾病的临床病理谱系，也就是TDP-43蛋白病。
