Walker Lary C, LeVine Harry
CNS Pharmacology, Pfizer Ann Arbor Laboratories, MI 48105, USA.
Curr Opin Investig Drugs. 2002 May;3(5):782-7.
The abnormal conformation and assembly of proteins is a probable cause of many degenerative diseases of old age. These proteopathies include such clinically disparate neurological disorders as Alzheimer's disease. Parkinson's disease and Creutzfeldt-Jakob disease, as well as a variety of non-neurological maladies. The involvement of protein pathology in these diseases is well established and we are beginning to understand the process whereby proteins self-assemble and injure tissues; however, we remain largely in the dark regarding the fundamental origins of the proteopathies. Our present knowledge suggests three broad therapeutic approaches to abrogating the proteopathic cascade: reduce the production of the offending proteins, prevent their self-assembly, or promote their removal.
蛋白质的异常构象和组装可能是许多老年退行性疾病的病因。这些蛋白质病包括临床上差异很大的神经疾病,如阿尔茨海默病、帕金森病和克雅氏病,以及各种非神经疾病。蛋白质病理学在这些疾病中的作用已得到充分证实,我们也开始了解蛋白质自我组装并损伤组织的过程;然而,对于蛋白质病的根本起源,我们仍知之甚少。我们目前的知识提示了三种消除蛋白质病级联反应的主要治疗方法:减少有害蛋白质的产生、防止它们自我组装或促进其清除。