Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, KY, 40536, USA; Lafora Epilepsy Cure Initiative, Epilepsy and Brain Metabolism Center, and Center for Structural Biology, University of Kentucky College of Medicine, Lexington, KY, 40536, USA; Institute for Research in Biomedicine (IRB Barcelona), 08028, Barcelona, Spain.
Univ. Grenoble Alpes, CNRS, CERMAV, F-38000, Grenoble, France.
Carbohydr Polym. 2020 Jul 15;240:116260. doi: 10.1016/j.carbpol.2020.116260. Epub 2020 Apr 14.
Abnormal carbohydrate structures known as polyglucosan bodies (PGBs) are associated with neurological disorders, glycogen storage diseases (GSDs), and aging. A hallmark of the GSD Lafora disease (LD), a fatal childhood epilepsy caused by recessive mutations in the EPM2A or EPM2B genes, are cytoplasmic PGBs known as Lafora bodies (LBs). LBs result from aberrant glycogen metabolism and drive disease progression. They are abundant in brain, muscle and heart of LD patients and Epm2a and Epm2b mice. LBs and PGBs are histologically reminiscent of starch, semicrystalline carbohydrates synthesized for glucose storage in plants. In this study, we define LB architecture, tissue-specific differences, and dynamics. We propose a model for how small polyglucosans aggregate to form LBs. LBs are very similar to PGBs of aging and other neurological disorders, and so these studies have direct relevance to the general understanding of PGB structure and formation.
异常的碳水化合物结构，称为多聚糖体 (PGBs)，与神经紊乱、糖原贮积疾病 (GSDs) 和衰老有关。GSD 拉佛拉病 (LD) 的一个特征是细胞质 PGBs，称为拉佛拉体 (LBs)，这是一种由 EPM2A 或 EPM2B 基因突变引起的致命儿童癫痫。LBs 是由异常的糖原代谢引起的，并导致疾病的进展。它们在 LD 患者的大脑、肌肉和心脏以及 Epm2a 和 Epm2b 小鼠中大量存在。LBs 和 PGBs 在组织学上类似于淀粉，这是一种半结晶的碳水化合物，用于植物的葡萄糖储存。在这项研究中，我们定义了 LB 的结构、组织特异性差异和动态。我们提出了一个关于小多聚糖如何聚集形成 LBs 的模型。LBs 与衰老和其他神经紊乱的 PGBs 非常相似，因此这些研究对于普遍理解 PGB 的结构和形成具有直接的意义。
