NOVEL USES OF SODIUM 4-PHENYLBUTYRATE (4 PBA) AND THE PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF
    4.
    发明公开
    NOVEL USES OF SODIUM 4-PHENYLBUTYRATE (4 PBA) AND THE PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF 审中-公开
    4-苯基丁酸钠(4 PBA)和药学上可接受的盐的新用途

    公开(公告)号:EP2272515A1

    公开(公告)日:2011-01-12

    申请号:EP09719846.9

    申请日:2009-03-06

    摘要: Novel uses for 4-phenylbutyrate (4PBA) and Its pharmaceutically acceptable salts
    The use of 4PBA in the manufacture of a medicament useful to treat cognitive disorders in dementias coursing with tauopathies is described.
    The treatment with 4PBA improves cognitive deficit in a classic murine experimental model of Alzheimer's Disease (AD) (Tg 2576) that is accompanied by decreasing levels of a marker characteristic to AD pathologies, such as phosphorylated Tau, and increasing levels in the synthesis of some synaptic plasticity marker proteins such as GluR1 and PSD95. As mediating mechanism for the therapeutic effect we propose a decreasing stress in the endoplasmic reticulum as manifested by increasing levels of the GRP78 protein. On the other hand its inhibiting effect on histone deacetylation and its involvement in chromatin remodeling facilitates protein synthesis processes, which improves synaptic plasticity.

    摘要翻译: 新用途4-苯(4PBA)及其药学上可接受的盐在制备药物有用的制造过程中使用的4PBA与tau蛋白病痴呆窃喜被描述为治疗认知障碍。 用4PBA治疗改善在阿尔茨海默病(AD)(TG 2576)的一个典型的鼠的实验模型中的认知缺陷确实伴随着降低的标记物特征的水平到AD的病理,检查如磷酸化tau和增加水平的某些合成 突触可塑性标记蛋白:如的GluR1和PSD95。 作为中介机构的治疗效果我们提出了一个降低应力的内质网由增加GRP78蛋白的水平表现出来。 在另一方面其抑制组蛋白脱乙酰化及其在染色质重塑参与便于蛋白质的合成方法,从而提高突触可塑性效果。