Novel insights into the pathogenesis of DYT1 dystonia from induced patient-derived neurons

Baojin Ding

摘要：Dystonia is a common movement disorder characterized by sustained or intermittent muscle contractions causing abnormal movements and/or postures (Keller Sarmiento and Mencacci, 2021). The dystonic syndromes are classified as primary dystonia (dystonia is the only motor feature without tremor) and the secondary dystonia (dystonia is combined with other movement disorders, such as Parkinsonism). Based on the age of onset, dystonias are also dichotomously classified as childhood onset or adulthood onset. The distribution of affected body parts may change over time and progressively spread of dystonia to previously uninvolved sites. Because the clinical characteristics and underlying causes of dystonia are very heterogeneous, the pathological mechanisms of dystonia remain largely unknown. The diagnosis and etiological definition of this disorder remain challenges. The current therapies, such as anticholinergics, intramuscular botulinum toxin injection and deep brain stimulation, are largely symptom-based and only partially satisfactory (Balint et al., 2018). The childhood-onset torsin dystonia, also called DYT1 dystonia, represents the most frequent and severe form of hereditary primary dystonia, providing an excellent example to understand the pathogenesis of this disease (Gonzalez-Alegre, 2019; Keller Sarmiento and Mencacci, 2021).