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淀粉样变性与神经退行性疾病:现有治疗方法与新的药理学选择。

Amyloidosis and neurodegenerative diseases: current treatments and new pharmacological options.

机构信息

Académie Nationale de Médecine Paris, Paris, France.

出版信息

Pharmacology. 2010;85(1):1-17. doi: 10.1159/000259044. Epub 2009 Nov 18.

Abstract

Most neurodegenerative diseases share several clinical, genetic and pathophysiological features, and an irreversible evolution as well. They are characterized by an endogenous production of abnormal proteins called amyloid proteins (AP), which are not hydrosoluble, form depots, and are only partly cleared by autophagy and the ubiquitin-protease system. Despite their different structures, they are probably generated by a common pathological pathway, a misfolding process. This hypothesis suggests a common pharmacological approach, which can consist of either the blockade of the misfolding process, the elimination of AP or both. The currently validated treatments are mostly palliative ones, trying to supplant the function of destroyed neurons. New trends involve the regulation of the cerebral cholesterol metabolism and the preservation of neuron mitochondrial functions. Special attention is given to already marketed drugs used for other indications, which are also able to act on neurodegeneration.

摘要

大多数神经退行性疾病具有相似的临床、遗传和病理生理学特征,且呈不可逆转的进展。其特征是内源性产生不溶于水的异常蛋白,称为淀粉样蛋白(amyloid protein,AP),这些蛋白形成沉积物,只能部分通过自噬和泛素蛋白酶系统清除。尽管它们的结构不同,但可能是由共同的病理途径——错误折叠过程产生的。该假说提示一种共同的药理学方法,包括阻断错误折叠过程、消除 AP 或两者兼而有之。目前验证的治疗方法大多是姑息性的,试图替代已破坏神经元的功能。新的趋势涉及调节脑内胆固醇代谢和维持神经元线粒体功能。特别关注已用于其他适应证的市售药物,这些药物也可能对神经退行性变起作用。

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