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Abstract：
Multisystem proteinopathy (MSP) is a pleiotropic group of inherited disorders that cause neurodegeneration, myopathy, and bone disease, and share common pathophysiology. Originally referred to as inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia (IBMPFD), attributed to mutations in the gene encoding valosin-containing protein (VCP), it has more recently been discovered that there are several other genes responsible for similar clinical and pathological phenotypes with muscle, brain, nerve, and bone involvement, in various combinations. These include heterogeneous nuclear ribonucleoprotein A2B1 and A1 (hnRNPA2B1, hnRNPA1), sequestosome 1 (SQSTM1), matrin 3 (MATR3), T-cell restricted intracellular antigen 1 (TIA1), and optineurin (OPTN), all of which share disruption of RNA stress granule function and autophagic degradation. This review will discuss each of the genes implicated in MSP, exploring the molecular pathogenesis, clinical features, current standards of care, and future directions for this diverse yet mechanistically linked spectrum of disorders.
摘要：
多系统蛋白病（MSP）是一组导致神经变性的遗传性疾病，肌病,和骨骼疾病，并具有共同的病理生理学。最初被称为与Paget骨和额颞叶痴呆（IBMPFD）相关的包涵体肌病，归因于编码含谷蛋白酶蛋白（VCP）的基因突变，最近发现，有几个其他基因负责与肌肉相似的临床和病理表型，大脑,神经,和骨骼受累，在各种组合中。这些包括异质核核糖核蛋白A2B1和A1（hnRNPA2B1，hnRNPA1），隔离体1(SQSTM1)，苦参素3(MATR3)，T细胞限制性细胞内抗原1（TIA1），和视神经磷酸酶（OPTN），所有这些都共享RNA应激颗粒功能的破坏和自噬降解。这篇综述将讨论MSP中涉及的每个基因，探索分子发病机制，临床特征,目前的护理标准，以及这种多样化但机械联系的疾病的未来方向。
