Riccardi Claudia, Perrone Lorena, Napolitano Filomena, Sampaolo Simone, Melone Mariarosa Anna Beatrice
Department of Chemical Sciences, University of Naples Federico II, via Cintia 21, I-80126 Naples, Italy.
Department of Advanced Medical and Surgical Sciences, 2nd Division of Neurology, Center for Rare Diseases and InterUniversity Center for Research in Neurosciences, University of Campania Luigi Vanvitelli, via Sergio Pansini 5, I-80131 Naples, Italy.
Cancers (Basel). 2020 Oct 13;12(10):2965. doi: 10.3390/cancers12102965.
Vitamin D is a fat-soluble steroid hormone playing a pivotal role in calcium and phosphate homeostasis as well as in bone health. Vitamin D levels are not exclusively dependent on food intake. Indeed, the endogenous production-occurring in the skin and dependent on sun exposure-contributes to the majority amount of vitamin D present in the body. Since vitamin D receptors (VDRs) are ubiquitous and drive the expression of hundreds of genes, the interest in vitamin D has tremendously grown and its role in different diseases has been extensively studied. Several investigations indicated that vitamin D action extends far beyond bone health and calcium metabolism, showing broad effects on a variety of critical illnesses, including cancer, infections, cardiovascular and autoimmune diseases. Epidemiological studies indicated that low circulating vitamin D levels inversely correlate with cutaneous manifestations and bone abnormalities, clinical hallmarks of neurofibromatosis type 1 (NF1). NF1 is an autosomal dominant tumour predisposition syndrome causing significant pain and morbidity, for which limited treatment options are available. In this context, vitamin D or its analogues have been used to treat both skin and bone lesions in NF1 patients, alone or combined with other therapeutic agents. Here we provide an overview of vitamin D, its characteristic nutritional properties relevant for health benefits and its role in NF1 disorder. We focus on preclinical and clinical studies that demonstrated the clinical correlation between vitamin D status and NF1 disease, thus providing important insights into disease pathogenesis and new opportunities for targeted therapy.
维生素D是一种脂溶性类固醇激素，在钙和磷的稳态以及骨骼健康方面发挥着关键作用。维生素D水平并非完全依赖于食物摄入。实际上，皮肤中发生的内源性合成（依赖于阳光照射）对体内大部分维生素D的产生有贡献。由于维生素D受体（VDR）广泛存在并驱动数百种基因的表达，人们对维生素D的兴趣急剧增长，并且对其在不同疾病中的作用进行了广泛研究。多项研究表明，维生素D的作用远远超出骨骼健康和钙代谢领域，对包括癌症、感染、心血管疾病和自身免疫性疾病在内的多种重大疾病都有广泛影响。流行病学研究表明，循环维生素D水平低与1型神经纤维瘤病（NF1）的皮肤表现和骨骼异常呈负相关，而这些正是NF1的临床特征。NF1是一种常染色体显性肿瘤易感性综合征，会导致严重疼痛和发病，针对该病的治疗选择有限。在此背景下，维生素D或其类似物已被用于单独或与其他治疗药物联合治疗NF1患者的皮肤和骨骼病变。在此，我们概述维生素D、其与健康益处相关的独特营养特性及其在NF1疾病中的作用。我们重点关注临床前和临床研究，这些研究证明了维生素D状态与NF1疾病之间的临床相关性，从而为疾病发病机制提供了重要见解，并为靶向治疗提供了新机会。
