The Papillon–Lefèvre syndrome (PLS) is a rare autosomal recessive disorder caused by mutations in the Cathepsin C (CTSC) gene, characterized by periodontitis and palmoplantar hyperkeratosis. The main inflammatory deficiencies include oxidative stress and autophagic dysfunction. Mitochondria are the main source of reactive oxygen species; their impaired function is related to skin diseases and periodontitis. The mitochondrial function has been evaluated in PLS and mitochondria have been targeted as a possible treatment for PLS. We show for the first time an important mitochondrial dysfunction associated with increased oxidative damage of mtDNA, reduced CoQ10 and mitochondrial mass and aberrant morphologies of the mitochondria in PLS patients. Mitochondrial dysfunction, determined by oxygen consumption rate (OCR) in PLS fibroblasts, was treated with CoQ10 supplementation, which determined an improvement in OCR and a remission of skin damage in a patient receiving a topical administration of a cream enriched with CoQ10 0.1%. We provide the first evidence of the role of mitochondrial dysfunction and CoQ10 deficiency in the pathophysiology of PLS and a future therapeutic option for PLS.

中文翻译：

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线粒体在Papillon-Lefèvre皮肤病治疗中的潜在作用

Papillon-Lefèvre综合征（PLS）是一种罕见的常染色体隐性遗传疾病，由组织蛋白酶C（CTSC）基因突变引起，特征是牙周炎和掌plant角化过度。主要的炎症缺陷包括氧化应激和自噬功能障碍。线粒体是活性氧的主要来源。它们的功能受损与皮肤疾病和牙周炎有关。线粒体功能已在PLS中进行了评估，线粒体已被定位为PLS的可能治疗方法。我们首次显示了重要的线粒体功能异常与mtDNA氧化损伤增加，CoQ10和线粒体质量减少以及PLS患者线粒体的形态异常有关。线粒体功能障碍，由PLS成纤维细胞的耗氧率（OCR）确定，辅酶Q10补充剂治疗后，确定接受局部施用富含0.1％辅酶Q10的面霜的患者的OCR改善和皮肤损伤缓解。我们提供线粒体功能障碍和辅酶Q10缺乏在PLS病理生理中的作用的初步证据，以及PLS的未来治疗选择。