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首页> 外文期刊>The journal of clinical psychiatry >Schizophrenia: Mechanism of action of current and novel treatments
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Schizophrenia: Mechanism of action of current and novel treatments

机译：精神分裂症：目前和新疗法的作用机理

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Introduction: Bone loss occurs in many diseases, including osteoporosis, rheumatoid arthritis and periodontal disease. For osteoporosis alone, it is estimated that 75 million people are afflicted worldwide, with high risks of fractures and increased morbidity and mortality. The demand for treatment consumes an ever-increasing share of healthcare resources. Successive generations of antiresorptive bisphosphonate drugs have reduced side effects, minimized frequency of dosing, and increased efficacy in halting osteoporotic bone loss, but their shortcomings have remained significant to the extent that a monoclonal antibody antiresorptive has recently taken a significant market share. Yet this latter, paradigm-shifting approach has its own drawbacks. Areas covered: This review summarizes recent literature on bone-remodeling cell and molecular biology and the background for existing approaches and emerging therapeutics and targets for treating osteoporosis. The authors discuss vacuolar H+-ATPase (V-ATPase) molecular biology and the recent advances in targeting the osteoclast ruffled-border V-ATPase (ORV) for the development of novel antiresorptive drugs. They also cover examples from the V-ATPase-targeted drug discovery literature, including conventional molecular biology methods, in silico drug discovery, and gene therapy in more detail as proofs of concept. Expert opinion: Existing therapeutic options for osteoporosis have limitations and inherent drawbacks. Thus, the search for novel approaches to osteoporosis drug discovery remains relevant. Targeting the ORV may be one of the more selective means of regulating bone resorption. Furthermore, this approach may be effective without removing active osteoclasts from the finely balanced osteoclast-osteoblast coupling required for normal bone remodeling.
机译：简介：骨丢失发生在许多疾病中，包括骨质疏松症，类风湿关节炎和牙周疾病。仅就骨质疏松症而言，据估计全世界有7500万人受其折磨，其骨折风险很高，发病率和死亡率也有所增加。对治疗的需求消耗了越来越多的医疗资源。连续几代的抗吸收性双膦酸盐药物具有减少的副作用，最小的给药频率以及增加的抑制骨质疏松性骨质流失的功效，但是它们的缺点仍然很明显，以至于单克隆抗体的抗吸收性最近占据了重要的市场份额。然而，后者的范式转换方法有其自身的缺点。涵盖领域：这篇综述总结了有关骨重塑细胞和分子生物学的最新文献以及现有的治疗骨质疏松的方法，新兴疗法和靶标的背景。作者讨论了液泡H + -ATPase（V-ATPase）分子生物学以及靶向破骨细胞皱纹V-ATPase（ORV）的最新进展以开发新型抗吸收药物。它们还涵盖了以V-ATPase为靶标的药物发现文献的例子，包括传统的分子生物学方法，计算机药物发现和基因治疗，作为概念验证的更多细节。专家意见：骨质疏松症的现有治疗选择具有局限性和固有缺陷。因此，寻找新的方法来发现骨质疏松症的药物仍然很重要。靶向ORV可能是调节骨吸收的更具选择性的手段之一。此外，这种方法在不从正常骨骼重塑所需的精细平衡的破骨细胞-成骨细胞偶联中去除活性破骨细胞的情况下可能是有效的。

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