Primary dystonia: molecules and mechanisms.
Primary dystonia: molecules and mechanisms.
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DOI：
10.1038/nrneurol.2009.160
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发表时间：
2009-11
影响因子：
38.1
通讯作者：
Dauer, William T.
中科院分区：
文献类型：
--
作者：
Tanabe, Lauren M.;Kim, Connie E.;Alagem, Noga;Dauer, William T.
原发性肌张力障碍的特征是反映运动系统功能受损的异常、不自主的扭转和转动运动。张力障碍的大脑似乎正常，因为它不包含明显的病变或神经变性的证据，但功能性脑成像发现异常涉及皮层，纹状体和小脑，扩散张量成像表明小脑丘脑皮质回路的白色物质束存在微结构缺陷。临床电生理学研究表明，张力障碍的中枢神经系统表现出过度活跃的可塑性-可能与抑制性神经传递不足-在一系列的脑结构，以及脊髓。因此，肌张力障碍最好被概念化为运动回路障碍，而不是特定大脑结构的异常。上述异常都不能是严格的因果关系，因为它们不限于CNS的区域，而临床上受影响的身体部位，并且在看似健康的患者中发现肌张力障碍相关突变。对肌张力障碍相关基因的研究有望帮助研究人员解开从分子到细胞再到系统异常的事件链。例如，DYT 1突变导致内质网-核膜内膜系统异常。其他肌张力障碍相关基因产物通过内质网运输，提示原发性肌张力障碍潜在的细胞生物学主题。
Primary dystonia is characterized by abnormal, involuntary twisting and turning movements that reflect impaired motor system function. The dystonic brain seems normal, in that it contains no overt lesions or evidence of neurodegeneration, but functional brain imaging has uncovered abnormalities involving the cortex, striatum and cerebellum, and diffusion tensor imaging suggests the presence of microstructural defects in white matter tracts of the cerebellothalamocortical circuit. Clinical electrophysiological studies show that the dystonic CNS exhibits hyperactive plasticity—perhaps related to deficient inhibitory neurotransmission—in a range of brain structures, as well as the spinal cord. Dystonia is, therefore, best conceptualized as a motor circuit disorder, rather than an abnormalcy of a particular brain structure. None of the aforementioned abnormalities can be strictly causal, as they are not limited to regions of the CNS subserving clinically affected body parts, and are found in seemingly healthy patients with dystonia-related mutations. The study of dystonia-related genes will, hopefully, help researchers to unravel the chain of events from molecular to cellular to system abnormalities. DYT1 mutations, for example, cause abnormalities within the endoplasmic reticulum–nuclear envelope endomembrane system. Other dystonia-related gene products traffic through the endoplasmic reticulum, suggesting a potential cell biological theme underlying primary dystonia.
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