了解杜氏肌营养不良相关的脑部病理。

IF 3.3 3区 医学 Q2 CELL BIOLOGY
Disease Models & Mechanisms Pub Date : 2025-07-01 Epub Date: 2025-08-01 DOI:10.1242/dmm.052302
Minou A T Verhaeg, Rosanne Govaarts, Maaike van Putten
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引用次数: 0

摘要

最常见的神经肌肉疾病,杜氏肌营养不良症(DMD),是由DMD基因突变引起的,导致缺乏肌营养不良蛋白。除了严重和进行性肌肉萎缩外,一部分DMD患者在很大程度上还会出现行为和认知缺陷,包括智商较低,以及神经系统合并症,如自闭症谱系障碍、强迫症和注意缺陷多动障碍。DMD患者的神经影像学研究已经确定了广泛的病理,包括结构、生理和结缔组织的改变。DMD小鼠模型表现出许多与DMD相关的行为特征,包括焦虑、社交缺陷和学习障碍,并已被用于研究DMD脑病理。虽然目前还没有治疗DMD脑部病理的方法,但正在开发遗传方法来恢复肌营养不良蛋白的表达。特别地,外显子跳跃方法在改善某些dmd相关的临床前行为缺陷方面显示出希望。然而,产后恢复参与神经发育的肌营养不良蛋白亚型的治疗潜力尚不清楚。此外,诸如低肌营养不良蛋白恢复功效和从DMD小鼠模型到临床的可转译性等挑战仍有待解决。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Understanding Duchenne muscular dystrophy-associated brain pathology.

The most common neuromuscular disorder, Duchenne muscular dystrophy (DMD), is caused by mutations in the DMD gene, resulting in a lack of dystrophin. In addition to severe and progressive muscle wasting, a subset of individuals with DMD experience, to largely varying extents, behavioural and cognitive deficits, including a lower IQ, and neurological comorbidities, such as autism spectrum disorder, obsessive compulsive disorder and attention deficit hyperactivity disorder. Neuroimaging studies in individuals with DMD have identified widespread pathology, including structural, physiological and connective alterations. DMD mouse models exhibit a number of DMD-associated behavioural traits, including anxiety, social deficits and learning disabilities, and have been used to investigate DMD brain pathology. Although there are currently no therapies to treat DMD brain pathology, genetic approaches are being developed to restore dystrophin expression. In particular, the exon skipping approach shows promise in ameliorating certain DMD-associated behavioural deficits in preclinical settings. However, the therapeutic potential of postnatal restoration of dystrophin isoforms involved in neurodevelopment is unknown. Furthermore, challenges such as low dystrophin restoration efficacy and translatability from DMD mouse models to the clinic remain to be addressed.

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来源期刊
Disease Models & Mechanisms
Disease Models & Mechanisms 医学-病理学
CiteScore
6.60
自引率
7.00%
发文量
203
审稿时长
6-12 weeks
期刊介绍: Disease Models & Mechanisms (DMM) is an online Open Access journal focusing on the use of model systems to better understand, diagnose and treat human disease.
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