The molecular basis of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum.
The molecular basis of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum.
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DOI：
10.3109/07853890.2012.665471
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发表时间：
2012-12
影响因子：
4.4
通讯作者：
Van Broeckhoven C
中科院分区：
文献类型：
--
作者：
Van Langenhove T;van der Zee J;Van Broeckhoven C
越来越多的证据表明，额颞叶变性（FTLD）和肌萎缩侧索硬化（ALS）代表了神经退行性疾病的连续谱系。在相当比例的患者中，FTLD并发ALS，并且神经心理学研究表明，多达50%的ALS患者存在额颞叶功能障碍。最近，神经病理学和分子遗传学的进展开始揭示所观察到的临床并发情况的生物学基础。TDP - 43和FUS已被发现是FTLD和ALS中的关键病理蛋白。最近发现基因C9orf72中的病理性六核苷酸重复扩增是FTLD和ALS的常见病因，最终证实了这两种乍一看不同的神经退行性疾病之间的关联。TARDBP、FUS和VCP基因的突变先前已与FTLD - ALS谱系的不同表型相关联，尽管在这些情况下，谱系的某一端占主导。这些发现一方面为重叠提供了证据，另一方面也强调了FTLD和ALS在病因上是多样的。在这篇综述中，我们回顾了支持FTLD - ALS谱系存在的最新进展，特别强调了分子遗传学方面。
There is increasing evidence that frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) represent a continuum of neurodegenerative diseases. FTLD is complicated by ALS in a significant proportion of patients, and neuropsychological studies have demonstrated frontotemporal dysfunction in up to 50% of ALS patients. More recently, advances in neuropathology and molecular genetics have started to disclose the biological basis for the observed clinical concurrence. TDP-43 and FUS have been discovered as key pathological proteins in both FTLD and ALS. The most recent discovery of a pathological hexanucleotide repeat expansion in the gene C9orf72 as a frequent cause of both FTLD and ALS has eventually confirmed the association of these two at first sight distinct neurodegenerative diseases. Mutations in the TARDBP, FUS, and VCP genes had previously been associated with different phenotypes of the FTLD-ALS spectrum, although in these cases one end of the spectrum predominates. Whilst on the one hand providing evidence for overlap, these discoveries have also highlighted that FTLD and ALS are etiologically diverse. In this review, we review the recent advances that support the existence of an FTLD-ALS spectrum, with particular emphasis on the molecular genetic aspect.
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