The Pharmacology of CD38/NADase: An Emerging Target in Cancer and Diseases of Aging.
The Pharmacology of CD38/NADase: An Emerging Target in Cancer and Diseases of Aging.
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DOI：
10.1016/j.tips.2018.02.001
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发表时间：
2018-04
影响因子：
13.8
通讯作者：
van Schooten W
中科院分区：
文献类型：
--
作者：
Chini EN;Chini CCS;Espindola Netto JM;de Oliveira GC;van Schooten W
最近的报道表明，组织中NAD的细胞内水平随着年龄的增长而下降，旨在增加细胞NAD水平的治疗可能对许多与年龄相关的疾病有有益的影响。CD38蛋白（CLUSTER OF DIFFERENTIATION 38）是一种降解NAD并调节细胞内稳态的多功能酶。在生理水平上，CD38参与调节代谢，并参与多种疾病的发病机制，包括：衰老、肥胖、糖尿病、心脏病、哮喘和炎症。有趣的是，许多这些功能是由CD38酶活性介导的。此外，CD38也被确定为血液学癌症（如多发性骨髓瘤）的细胞表面标志物，并且一种细胞毒性抗CD38抗体已被FDA批准用于该疾病。虽然这是一个显著的进展，但用细胞毒性抗CD38抗体杀死CD38阳性肿瘤细胞只是靶向CD38的潜在药理用途之一。本文综述了CD38酶的生物学特性和针对CD38的药理学工具的发展现状，并探讨了这些药物如何代表一种治疗人类疾病的新方法，包括癌症、代谢性疾病和衰老疾病。
Recent reports indicate that intracellular levels of NAD decline in tissues during chronological aging, and that therapies aim at increasing cellular NAD levels could have beneficial effects in many age-related diseases. The protein CD38 (CLUSTER OF DIFFERENTIATION 38) is a multifunctional enzyme that degrades NAD and modulates cellular NAD homeostasis. At the physiological level, CD38 has been implicated in the regulation of metabolism, and the pathogenesis of multiple conditions including: aging, obesity, diabetes, heart disease, asthma and inflammation. Interestingly, many of these functions are mediated by the CD38 enzymatic activity. In addition, CD38 has also been identified as a cell surface marker in hematologic cancers such as multiple myeloma, and a cytotoxic anti-CD38 antibody has been approved by the FDA for use in this disease. Although this is a remarkable development, killing CD38-positive tumor cells with cytotoxic anti-CD38 antibodies is only one of the potential pharmacological uses of targeting CD38. The present review discusses the biology of the CD38 enzyme and the current state of development of pharmacological tools aim at CD38 and explores how these agents may represent a novel approach to treat human conditions including cancer, metabolic diseases and diseases of aging.
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DOI：
10.1126/science.aad5168
发表时间：
2016-06-17
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cambronne XA;Stewart ML;Kim D;Jones-Brunette AM;Morgan RK;Farrens DL;Cohen MS;Goodman RH
通讯作者：
Goodman RH
影响因子：
7.3
作者：
Becherer, J. David;Boros, Eric E.;Ulrich, John C.
通讯作者：
Ulrich, John C.
影响因子：
16
作者：
Avalos, JL;Bever, KM;Wolberger, C
通讯作者：
Wolberger, C
影响因子：
13.5
作者：
Deshpande DA;Guedes AGP;Lund FE;Subramanian S;Walseth TF;Kannan MS
通讯作者：
Kannan MS
影响因子：
29
作者：
Chatterjee S;Daenthanasanmak A;Chakraborty P;Wyatt MW;Dhar P;Selvam SP;Fu J;Zhang J;Nguyen H;Kang I;Toth K;Al-Homrani M;Husain M;Beeson G;Ball L;Helke K;Husain S;Garrett-Mayer E;Hardiman G;Mehrotra M;Nishimura MI;Beeson CC;Bupp MG;Wu J;Ogretmen B;Paulos CM;Rathmell J;Yu XZ;Mehrotra S
通讯作者：
Mehrotra S