Recessive mutations in human N-glycanase 1 (NGLY1) cause a multisystem disorder with various phenotypes including global developmental delay. One of the models utilized to understand the biology of NGLY1 and the pathophysiology of NGLY1 deficiency is Drosophila melanogaster, a well-established, genetically tractable organism broadly used to study various biological processes and human diseases. Loss of the Drosophila NGLY1 homolog (Pngl) causes a host of phenotypes including developmental delay and lethality. Phenotypic, transcriptomic and genome-wide association analyses on Drosophila have revealed links between NGLY1 and several critical developmental and cellular pathways/processes. Further, repurposing screens of FDA-approved drugs have identified potential candidates to ameliorate some of the Pngl mutant phenotypes. Here, we will summarize the insights gained into the functions of NGLY1 from Drosophila studies. We hope that the current review article will encourage additional studies in Drosophila and other model systems towards establishing a therapeutic strategy for NGLY1 deficiency patients.

中文翻译：

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追踪 NGLY1 的足迹：来自果蝇的见解

人类N-聚糖酶 1 ( NGLY1 ) 的隐性突变导致具有各种表型的多系统疾病，包括全球发育迟缓。用于了解 NGLY1 生物学和 NGLY1 缺乏症的病理生理学的模型之一是黑腹果蝇，它是一种成熟的、遗传易处理的生物体，广泛用于研究各种生物过程和人类疾病。果蝇 NGLY1同源物 ( Pngl ) 的缺失会导致许多表型，包括发育迟缓和致死性。果蝇的表型、转录组和全基因组关联分析揭示了 NGLY1 与几个关键的发育和细胞途径/过程之间的联系。此外，FDA 批准药物的再利用筛选已经确定了改善某些Pngl突变表型的潜在候选药物。在这里，我们将总结从果蝇研究中获得的对 NGLY1 功能的见解。我们希望当前的评论文章将鼓励对果蝇和其他模型系统进行更多研究，以建立针对 NGLY1 缺乏症患者的治疗策略。