Mitochondrial dysfunction is a key determinant of the rare disease lymphangioleiomyomatosis and provides a novel therapeutic target
Mitochondrial dysfunction is a key determinant of the rare disease lymphangioleiomyomatosis and provides a novel therapeutic target
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DOI：
10.1038/s41388-018-0625-1
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发表时间：
2019-04-18
期刊：
影响因子：
8
通讯作者：
Pongracz, J. E.
中科院分区：
文献类型：
--
作者：
Abdelwahab, E. M. M.;Pal, S.;Pongracz, J. E.
淋巴管平滑肌瘤病（LAM）是一种罕见的进行性全身性疾病，主要影响育龄期年轻女性。肺功能恶化是由肺间质中非典型平滑肌样LAM细胞的肿瘤生长驱动的，其导致囊性肺破坏和自发性气胸。用于预防疾病进展的治疗选择是有限的，并且通常以肺移植暂时延迟不可避免的下降而结束。为了确定这种严重孤儿病的新治疗策略，我们对患者来源的细胞系进行了基于阵列的代谢分子分析。我们的研究结果表明，LAM细胞中的线粒体生物合成和线粒体功能障碍提供了一个新的治疗靶点。
Lymphangioleiomyomatosis (LAM) is a rare and progressive systemic disease affecting mainly young women of childbearing age. A deterioration in lung function is driven by neoplastic growth of atypical smooth muscle-like LAM cells in the pulmonary interstitial space that leads to cystic lung destruction and spontaneous pneumothoraces. Therapeutic options for preventing disease progression are limited and often end with lung transplantation temporarily delaying an inevitable decline. To identify new therapeutic strategies for this crippling orphan disease, we have performed array based and metabolic molecular analysis on patient-derived cell lines. Our results point to the conclusion that mitochondrial biogenesis and mitochondrial dysfunction in LAM cells provide a novel target for treatment.