Protein homeostasis and quality control, as balanced by synthesis and degradation, is critical to cellular health and normal cardiac function. Similar to amyloid-related neurodegenerative diseases, the familial forms of amyloid cardiomyopathy are characterized by protein aggregate accumulation in cardiomyocytes. These protein aggregates trigger proteotoxicity in cardiomyocytes, leading to cardiac remodeling and dysfunction.1 Beyond these familial forms of cardiomyopathies, protein aggregation is also a common and perhaps functionally significant pathological feature in the diseased hearts induced by a variety of pathological stressors, including pressure overload and ischemia.2,3 Therefore, understanding the pathogenic mechanisms of cardiac proteotoxicity induced by protein aggregation in cardiomyocytes could lead to significant progress to develop potential therapeutic interventions, not only for the rare cases of amyloid cardiomyopathies but also for the common forms of heart failure in general. Article, see p 604 In this issue, McLendon et al4 from Robbins’s laboratory performed an unbiased genome-wide screening to identify genes affecting protein aggregation in primary cardiomyocytes. Taking advantage of a previously established αB-Crystallin mutant protein (CryABR120G) which possesses a strong propensity to form desmin-related protein aggregates in cardiomyocytes,5,6 they developed a high-throughput screening platform to measure protein aggregation quantitatively based on fluorescent signal intensity from the exogenously expressed GFP (green fluorescent protein) CryAB …

中文翻译：

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通过Janus Kinase 1解开破碎的心

蛋白质的动态平衡和质量控制（通过合成和降解来平衡）对于细胞健康和正常的心脏功能至关重要。与淀粉样蛋白相关的神经退行性疾病相似，淀粉样蛋白心肌病的家族形式以心肌细胞中蛋白聚集为特征。这些蛋白质聚集体会触发心肌细胞的蛋白毒性，导致心脏重塑和功能障碍。1除了这些家族性的心肌病，蛋白质聚集体还是由多种病理性应激因素（包括压力超负荷）诱发的患病心脏的常见且功能上重要的病理特征和缺血。2,3因此，认识到心肌细胞中蛋白质聚集所引起的心脏蛋白毒性的致病机制，可能会导致开发潜在的治疗性干预方法取得重大进展，这不仅适用于淀粉样蛋白性心肌病的罕见病例，而且适用于一般的心力衰竭。文章，请参阅第604页。在本期中，Robbins实验室的McLendon等人4进行了无偏见的全基因组筛选，以鉴定影响原代心肌细胞中蛋白质聚集的基因。利用先前建立的αB-Crystallin突变蛋白（CryABR120G），该蛋白具有在心肌细胞中形成结蛋白相关蛋白聚集体的强烈倾向5，