Nowak Bartosz, Kozlowska Emilia, Pawlik Weronika, Fiszer Agnieszka
Department of Medical Biotechnology, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland.
Mov Disord. 2023 Apr;38(4):526-536. doi: 10.1002/mds.29355. Epub 2023 Feb 21.
Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare, incurable genetic disease that belongs to the group of polyglutamine (polyQ) diseases. DRPLA is the most common in the Japanese population; however, its global prevalence is also increasing due to better clinical recognition. It is characterized by cerebellar ataxia, myoclonus, epilepsy, dementia, and chorea. DRPLA is caused by dynamic mutation of CAG repeat expansion in ATN1 gene encoding the atrophin-1 protein. In the cascade of molecular disturbances, the pathological form of atrophin-1 is the initial factor, which has not been precisely characterized so far. Reports indicate that DRPLA is associated with disrupted protein-protein interactions (in which an expanded polyQ tract plays a crucial role), as well as gene expression deregulation. There is a great need to design efficient therapy that would address the underlying neurodegenerative process and thus prevent or alleviate DRPLA symptoms. An in-depth understanding of the normal atrophin-1 function and mutant atrophin-1 dysfunction is crucial for this purpose. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
齿状核红核苍白球路易体萎缩症（DRPLA）是一种罕见的、无法治愈的遗传性疾病，属于多聚谷氨酰胺（polyQ）疾病组。DRPLA在日本人群中最为常见；然而，由于临床识别能力的提高，其全球患病率也在上升。它的特征是小脑共济失调、肌阵挛、癫痫、痴呆和舞蹈症。DRPLA是由编码萎缩素-1蛋白的ATN1基因中CAG重复序列扩增的动态突变引起的。在一系列分子紊乱中，萎缩素-1的病理形式是初始因素，到目前为止尚未得到精确表征。报告表明，DRPLA与蛋白质-蛋白质相互作用破坏（其中扩展的多聚谷氨酰胺序列起关键作用）以及基因表达失调有关。迫切需要设计有效的治疗方法来解决潜在的神经退行性过程，从而预防或减轻DRPLA症状。为此，深入了解正常萎缩素-1的功能和突变型萎缩素-1的功能障碍至关重要。© 2023作者。《运动障碍》由威利期刊有限责任公司代表国际帕金森病和运动障碍协会出版。
