Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Fondazione Santa Lucia, Rome, Italy.
Dipartimento di Scienze della Vita e della Sanità Pubblica, Università Cattolica del Sacro Cuore, Rome, Italy.
Adv Exp Med Biol. 2022;1382:71-84. doi: 10.1007/978-3-031-05460-0_5.
Muscular dystrophies are a complex group of inherited neuromuscular disorders that progressively lead to a loss of muscle fibers and mobility and muscle weakness; over time, they evolve to an increasing level of disability. Muscular dystrophies are mostly caused by genetic mutations in proteins responsible for maintaining sarcolemma structures, such as an absence or reductions of dystrophin expression, conditions which are strictly related to muscular disorders that affect most people with this disease. Along the years, with the recent advances in the understanding of muscular dystrophies, it has been shown that many changes in Post-Translational Modifications (PTMs) of muscle proteins are associated with muscular dystrophies, wherein pathogenic alterations in the modulation of these muscle proteins are directly related to the incidence of this disease. An increase in the identification of the genetic bases and molecular mechanisms involved in the most common form of muscular dystrophies, including PTMs changes, holds potential to develop new therapeutic approaches. In this chapter we will describe the most common muscular dystrophies and changes in PTM processes such as phosphorylation and glycosylation that are very important in the evolution of the disease, highlighting the lack of mass spectrometry-based (MS-based) studies of these PTMs, suggesting that the application of this technique could reveal important informations about the molecular mechanisms of muscular dystrophies.
肌肉萎缩症是一组复杂的遗传性神经肌肉疾病，它们会逐渐导致肌肉纤维和运动能力的丧失以及肌肉无力；随着时间的推移，它们会发展到越来越严重的残疾程度。肌肉萎缩症主要是由于负责维持肌膜结构的蛋白质中的遗传突变引起的，例如肌营养不良蛋白的缺失或减少，这些情况与影响大多数患有这种疾病的人的肌肉疾病密切相关。多年来，随着对肌肉萎缩症的理解的最新进展，已经表明肌肉蛋白的翻译后修饰（PTMs）的许多变化都与肌肉萎缩症有关，其中这些肌肉蛋白的调节中的致病改变与这种疾病的发生率直接相关。增加对最常见的肌肉萎缩症形式的遗传基础和分子机制的鉴定，包括 PTM 变化，有可能开发出新的治疗方法。在这一章中，我们将描述最常见的肌肉萎缩症和 PTM 过程的变化，如磷酸化和糖基化，这些变化在疾病的发展中非常重要，强调缺乏基于质谱的（MS 基）对这些 PTM 的研究，表明该技术的应用可能会揭示有关肌肉萎缩症分子机制的重要信息。
