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    • 5. 发明授权
    • Farnesyltransferase inhibitors for treatment of laminopathies, cellular aging and atherosclerosis
    • 用于治疗层状病毒,细胞衰老和动脉粥样硬化的法呢基转移酶抑制剂
    • US08257915B2
    • 2012-09-04
    • US12905838
    • 2010-10-15
    • Leslie B. GordonFrancis S. CollinsThomas GloverMichael W. GlynnBrian C. CapellAdrienne D. CoxChanning J. Der
    • Leslie B. GordonFrancis S. CollinsThomas GloverMichael W. GlynnBrian C. CapellAdrienne D. CoxChanning J. Der
    • C12Q1/00C12Q1/02
    • A61K31/4545A61K31/4709A61K45/06C07K14/47C12Q1/6883C12Q1/6886C12Q2600/136C12Q2600/156G01N33/68G01N2333/91171G01N2500/04G01N2500/10
    • Although it can be farnesylated, the mutant lamin A protein expressed in Hutchinson Gilford Progeria Syndrome (HGPS) cannot be defarnesylated because the characteristic mutation causes deletion of a cleavage site necessary for binding the protease ZMPSTE24 and effecting defarnesylation. The result is an aberrant farnesylated protein (called “progerin”) that alters normal lamin A function as a dominant negative, as well as assuming its own aberrant function through its association with the nuclear membrane. The retention of farnesylation, and potentially other abnormal properties of progerin and other abnormal lamin gene protein products, produces disease. Farnesyltransferase inhibitors (FTIs) (both direct effectors and indirect inhibitors) will inhibit the formation of progerin, cause a decrease in lamin A protein, and/or an increase prelamin A protein. Decreasing the amount of aberrant protein improves cellular effects caused by and progerin expression. Similarly, treatment with FTIs should improve disease status in progeria and other laminopathies. In addition, elements of atherosclerosis and aging in non-laminopathy individuals will improve after treatment with farnesyltransferase inhibitors.
    • 虽然它可以被法呢基化,但是在Hutchinson Gilford Progeria综合征(HGPS)中表达的突变体蛋白A蛋白质不能被脱甲酰化,因为特征性突变导致缺失结合蛋白酶ZMPSTE24所必需的切割位点并进行脱甲酰化。 结果是异常的法呢基蛋白(称为“progerin”),其改变正常的lamin A功能作为显性阴性,并且通过与核膜的结合来假设其自身的异常功能。 法呢基化的保留,以及progerin和其他异常的lamin基因蛋白产物的潜在的其他异常性质产生疾病。 法尼基转移酶抑制剂(FTIs)(直接作用剂和间接抑制剂)将抑制progerin的形成,导致lamin A蛋白的降低和/或增加的prelamin A蛋白。 减少异常蛋白质的量会改善由progerin表达引起的细胞效应。 同样,FTIs治疗应改善progeria和其他层层病的疾病状况。 此外,在用法呢基转移酶抑制剂治疗后,动脉粥样硬化和非层状病变个体的老化将会改善。
    • 6. 发明申请
    • Hand mounted holiday tester
    • 手提假日测试仪
    • US20050057258A1
    • 2005-03-17
    • US10942639
    • 2004-09-16
    • Jerry ColahanThomas Glover
    • Jerry ColahanThomas Glover
    • G01N27/20G01R31/00
    • G01N27/205
    • A hand mounted holiday tester includes a control unit with electrical sensing apparatus for detecting a completed circuit between a positive pole and a negative pole of the control unit. The tester further includes a hand receiving mitten, constructed of non-electrically conductive, flexible material with a front surface generally adjacent and parallel to the palm of a hand in the mitten. A flat sponge is fixedly attached to the front surface of the mitten with the front surface of the sponge substantially parallel to the front surface of the mitten. An electrical contact to the sponge includes a loop of wire embedded in the sponge and electrically coupled to one of the positive pole and the negative pole of the control unit.
    • 手持假日测试仪包括具有用于检测控制单元的正极和负极之间的完整电路的电气感测装置的控制单元。 该测试器还包括由不导电的柔性材料制成的手接收手套,其前表面大致相邻并平行于手套中的手掌。 扁平海绵固定地附接到手套的前表面,海绵的前表面基本上平行于手套的前表面。 与海绵的电接触包括嵌入海绵中的电线环,并电耦合到控制单元的正极和负极之一。