Dystonia is a clinically, genetically, and biologically heterogeneous hyperkinetic movement disorder caused by the dysfunctional activity of neural circuits involved in motor control. Our understanding of the molecular mechanisms underlying dystonia pathogenesis has tremendously grown thanks to the accelerated discovery of genes associated with monogenic dystonias (DYT-genes). Genetic discoveries, together with the development of a growing number of cellular and animal models of genetic defects responsible for dystonia, are allowing the identification of several areas of functional convergence among the protein products of multiple DYT-genes. Furthermore, unexpected functional links are being discovered in the downstream pathogenic molecular mechanisms of DYT-genes that were thought to be unrelated based on their primary molecular functions. Examples of these advances are the recognition that multiple DYT-genes are involved in (1) endoplasmic reticulum function and regulation of the integrated stress response (ISR) through Eukaryotic initiation factor 2 alpha signaling; (2) gene transcription modulation during neurodevelopment; (3) pre-and post-synaptic nigrostriatal dopaminergic signaling; and (4) presynaptic neurotransmitter vesicle release. More recently, genetic defects in the endo-lysosomal and autophagy pathways have also been implicated in the molecular pathophysiology of dystonia, suggesting the existence of mechanistic overlap with other movement disorders, such as Parkinson’s disease. Importantly, the recognition that multiple DYT-genes coalesce in shared biological pathways is a crucial advance in our understanding of dystonias and will aid in the development of more effective therapeutic strategies by targeting these convergent molecular pathways.

肌张力障碍是一种临床、遗传和生物学异质性多动性运动障碍，由参与运动控制的神经回路的功能失调引起。由于与单基因肌张力障碍相关的基因（DYT 基因）的加速发现，我们对肌张力障碍发病机制的分子机制的理解得到了极大的发展。遗传发现，以及越来越多的导致肌张力障碍的遗传缺陷的细胞和动物模型的发展，使得能够识别多个 DYT 基因的蛋白质产物之间的几个功能融合区域。此外，在 DYT 基因的下游致病分子机制中发现了意想不到的功能联系，这些机制被认为是基于其主要分子功能无关的。这些进步的例子是认识到多个 DYT 基因参与 (1) 内质网功能和通过真核起始因子 2 α 信号传导对综合应激反应 (ISR) 的调节；(2) 神经发育过程中的基因转录调控；(3) 突触前和突触后黑质纹状体多巴胺能信号；(4) 突触前神经递质囊泡释放。最近，内溶酶体和自噬途径中的遗传缺陷也与肌张力障碍的分子病理生理学有关，这表明与其他运动障碍（如帕金森病）存在机制重叠。重要的，