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首页> 外文期刊>Life sciences >PHARMACOLOGIC INHIBITION OF TRANSGLUTAMINASE-INDUCED CROSS-LINKING OF ALZHEIMERS AMYLOID BETA-PEPTIDE
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PHARMACOLOGIC INHIBITION OF TRANSGLUTAMINASE-INDUCED CROSS-LINKING OF ALZHEIMERS AMYLOID BETA-PEPTIDE

机译：谷氨酰胺淀粉β-肽经转谷氨酰胺酶诱导的交联的药理学抑制作用

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The brain of Alzheimer's disease (AD) patients contains deposits of amyloid beta-peptide (A beta). Recent studies have shown that A beta is a substrate for tissue transglutaminase (TGase), which induces the formation of cross-linked dimers and polymers, and that tacrine, indomethacin and deferoxamine, which have widely different chemical structures, attenuate the progression of symptoms of AD. This report evaluated the potential of a total of ten different pharmacological agents to inhibit TGase-induced cross-linking of A beta, including known TGase inhibitors (dansylcadaverine, spermine), non-steroidal anti-inflammatory drugs (indomethacin, meclofenamic acid, diflunisal salicylic acid), monoamine oxidase inhibitors (tranylcypromine, phenelzine), an acetylcholinesterase inhibitor (tacrine), and an iron chelating agent (deferoxamine). All but one (salicylic acid) of these ten agents had an inhibitory effect on TGase-induced A beta cross-linking. These results suggest that inhibition of TGase-induced cross-linking of A beta is a potential pharmacologic target for the treatment of AD. A method is also presented for the determination of percent inhibition of TGase-induced A beta cross-linking based on the separated monomer, dimer and polymer bands on SDS-PAGE gels. [References: 21]
机译：阿尔茨海默氏病（AD）患者的大脑含有淀粉样β肽（A beta）沉积物。最近的研究表明，Aβ是组织转谷氨酰胺酶（TGase）的底物，可诱导交联的二聚体和聚合物的形成，而他克林，吲哚美辛和去铁胺的化学结构差异很大，从而减轻了症状的发展。广告。该报告评估了总共十种不同药理剂抑制TGase诱导的A beta交联的潜力，包括已知的TGase抑制剂（丹磺胺，精胺），非甾体类抗炎药（吲哚美辛，甲氯芬那酸，双氟水杨酸）酸），单胺氧化酶抑制剂（反式环丙胺，苯乙嗪），乙酰胆碱酯酶抑制剂（他克林）和铁螯合剂（去铁胺）。这十种药物中除一种（水杨酸）外，其余所有对TGase诱导的Aβ交联均具有抑制作用。这些结果表明，抑制TGase诱导的Aβ交联是治疗AD的潜在药理学靶标。还提出了一种方法，用于基于SDS-PAGE凝胶上分离的单体，二聚体和聚合物带，确定TGase诱导的Aβ交联的抑制百分比。 [参考：21]

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