mTOR Signaling Cascade in Psoriatic Disease: Double Kinase mTOR Inhibitor a Novel Therapeutic Target.
mTOR Signaling Cascade in Psoriatic Disease: Double Kinase mTOR Inhibitor a Novel Therapeutic Target.
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DOI：
10.4103/0019-5154.123499
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发表时间：
2014-01
影响因子：
1.7
通讯作者：
Raychaudhuri SP
中科院分区：
文献类型：
--
作者：
Raychaudhuri SK;Raychaudhuri SP
在这个简短的交流中，我们提供了关于磷脂酰肌醇3-激酶（PI 3 K）-AKT-哺乳动物雷帕霉素靶蛋白（mTOR）激酶系统在银屑病疾病中的调节作用的见解。这是一个即将到来的活跃的研究领域，阐明银屑病疾病的炎症和增殖级联反应。为了提供对自身免疫性疾病发病机制的分子原理的理解的新维度，我们假设（i）自身免疫性疾病中细胞因子和生长因子的失调激活mTOR信号传导系统，以及（ii）激活的mTOR激酶系统是疾病过程的炎症/增殖级联的关键调节剂。为了支持这一假设，我们先前报道了已知对银屑病、银屑病关节炎和类风湿性关节炎至关重要的生长因子（神经生长因子（NGF）和血小板衍生生长因子（PDGF））和相关细胞因子（白介素（IL）-17，IL-22）激活mTOR信号传导系统。在这里，我们提供了我们最新的观察结果，即mTOR信号传导蛋白在银屑病皮肤中上调，并且我们进一步观察到银屑病关节炎的角质形成细胞（KC）和滑膜细胞（滑膜成纤维细胞（FLS））的增殖依赖于PI 3 K-AKT-mTOR激酶系统。据我们所知，我们是第一个探索mTOR信号蛋白的双激酶抑制剂是否具有治疗银屑病的潜力。在这里，我们将分享我们的观点，我们在这一领域的研究工作，以及我们将提供证据如何mTOR信号蛋白的双激酶抑制剂可以成为银屑病疾病的有效治疗剂。
In this short communication we are providing insight about the regulatory role of the phosphatidylinositol 3-kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) kinase system in psoriatic disease. This is an upcoming active research field in respect to elucidating the inflammatory and proliferative cascades of psoriatic disease. To provide a new dimension to the understandings of the molecular principles of the pathogenesis of autoimmune diseases, we hypothesized that (i) dysregulation of cytokines and growth factors in autoimmune diseases activate the mTOR signaling system and (ii) the activated mTOR kinase system is a key regulator of the inflammatory/proliferative cascades of the disease process. In support of this hypothesis we have earlier reported that growth factors (nerve growth factor (NGF) and platelet-derived growth factor (PDGF)) and relevant cytokines (interleukin (IL)-17, IL-22) known to be critical for psoriasis, psoriatic arthritis, and rheumatoid arthritis activate the mTOR signaling system. Here, we are providing our latest observations that the mTOR signaling proteins are upregulated in psoriatic skin and further we observed that proliferation of keratinocytes (KC) and synovial cells (synovial fibroblasts (FLS)) of psoriatic arthritis are dependent on the PI3K-AKT-mTOR kinase system. To our knowledge, we are the first to explore whether a double kinase inhibitor of mTOR signal proteins has a therapeutic potential for psoriatic disease. Here we will be sharing our views, our research work in this field and as well we will provide evidences how a double kinase inhibitor of mTOR signal proteins can be an effective therapeutic agent for psoriatic disease.
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影响因子：
4.8
作者：
Calautti, E;Li, J;Goetinck, PF
通讯作者：
Goetinck, PF
影响因子：
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Raychaudhuri, Siba P.
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通讯作者：
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