Different conditions, ranging from genetic mutation to post-translational modification,  result in the intracellular presence of misfolded or conformationally altered proteins. These abnormal proteins tend to organize in toxic oligomeric structures often resulting in cellular death. Alterations in the function of the surveillance systems that normally repair or remove abnormal proteins are the basis of many neurodegenerative disorders. In this review, we focus on such protein conformational disorders and on the role that altered function of intracellular proteolytic systems, in particular autophagy, plays in the evolution of these diseases. Using Parkinson disease as a main example, we recapitulate the different stages of this protein conformational disorder at the cellular level and relate them with changes in the different types of autophagy. Finally, we also comment on the effect that aggravating conditions, such as oxidative stress and aging, have on the functioning of the autophagic system and its ability to cope with altered proteins.

    从基因突变到翻译后修饰等不同条件均可引起细胞内的蛋白质出现错误折叠或者构象改变。这些异常蛋白质倾向于形成有毒的寡聚结构，并且常可导致细胞死亡。正常情况下机体监测系统具有修复或者消除异常蛋白质的作用，其功能的变化是许多神经变性疾病的基础。本综述中,我们集中在上述的蛋白质构象障碍和细胞内的蛋白水解系统功能改变，尤其是自噬，在疾病演变的作用。以帕金森病为主要范例,我们在细胞水平上概括了蛋白构象障碍在不同的阶段和不同类型的自噬类型的变化。最后,我们同样论述了氧化应激和老化等影响因素对自噬系统功能的影响和自噬系统处理异常蛋白质的能力。