The NADase enzyme CD38: an emerging pharmacological target for systemic sclerosis, systemic lupus erythematosus and rheumatoid arthritis.
The NADase enzyme CD38: an emerging pharmacological target for systemic sclerosis, systemic lupus erythematosus and rheumatoid arthritis.
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DOI：
10.1097/bor.0000000000000737
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发表时间：
2020-11
影响因子：
5.1
通讯作者：
Chini EN
中科院分区：
文献类型：
--
作者：
Peclat TR;Shi B;Varga J;Chini EN
在此，我们回顾了有关烟酰胺腺嘌呤二核苷酸（NAD⁺）代谢的新兴作用以及通过酶CD38导致的其功能失调在风湿性疾病发病机制中的近期文献。我们评估了在系统性硬化症（SSc）、系统性红斑狼疮（SLE）和类风湿关节炎（RA）的治疗中，以CD38为靶点改善与NAD⁺相关的代谢失衡和组织功能障碍的潜力。
在这篇综述中，我们将讨论新兴的基础、临床前和人体数据，这些数据表明CD38在SSc、SLE和RA中NAD⁺稳态失调方面的新作用。特别是，近期研究表明，作为NAD⁺分解代谢的主要酶之一，CD38的活性增加在SSc的持续性系统性纤维化发病机制中起作用，并且增加了SLE患者对感染的易感性。我们还将讨论近期的研究，这些研究表明一种细胞毒性CD38抗体能够促进清除参与产生RA抗体的浆细胞。
近期研究确定了提高NAD以治疗包括SSc、RA和SLE在内的风湿性疾病的潜在治疗方法，尤其关注将抑制CD38酶活性作为一个靶点。该领域未来的关键方向包括确定CD38酶活性相对于CD38结构作用在人类疾病中的细胞类型特异性和作用，以及以CD38为靶点的治疗的指标和潜在副作用。
Here we review recent literature on the emerging role of nicotinamide adenine dinucleotide (NAD+) metabolism and its dysfunction via the enzyme CD38 in the pathogenesis of rheumatologic diseases. We evaluate the potential of targeting CD38 to ameliorate NAD+-related metabolic imbalance and tissue dysfunction in the treatment of systemic sclerosis (SSc), systemic lupus erythematous (SLE), and rheumatoid arthritis (RA). In this review we will discuss emerging basic, pre-clinical and human data that point to the novel role of a CD38 in dysregulated NAD-homeostasis in SSc, SLE and RA. In particular, recent studies implicate increased activity of CD38, one of the main enzymes in NAD+-catabolism, in the pathogenesis of persistent systemic fibrosis in SSc, and increased susceptibility of SLE patients to infections. We will also discuss recent studies that demonstrate that a cytotoxic CD38 antibody can promote clearance of plasma cells involved in the generation of RA antibodies. Recent studies identify potential therapeutic approaches for boosting NAD to treat rheumatologic diseases including SSc, RA, and SLE, with particular attention to inhibition of CD38 enzymatic activity as a target. Key future directions in the field include the determination of the cell-type specificity and role of CD38 enzymatic activity versus CD38 structural roles in human diseases, as well as the indicators and potential side effects of CD38-targeted treatments.