Institute of Neuroimmunology, Slovak Academy of Sciences, Centre of Excellence for Alzheimer's Disease and Related Disorders, Dubravska cesta 9, 845 10, Bratislava, Slovak Republic.
Mol Neurobiol. 2013 Dec;48(3):516-32. doi: 10.1007/s12035-013-8440-8. Epub 2013 Mar 21.
Neurodegenerative foldopathies are characterized by aberrant folding of diseased modified proteins, which are major constituents of the intracellular and extracellular lesions. These lesions correlate with the cognitive and/or motor impairment seen in these diseases. The majority of the disease modified proteins in neurodegenerative foldopathies belongs to the group of proteins termed as intrinsically disordered proteins (IDPs). Several independent studies have showed that abnormal protein processing constitutes the key pathological feature of these disorders. The current review focuses on protein truncation as a common denominator of neurodegenerative foldopathies, which is considered to be the major driving force behind the pathological metamorphosis of brain IDPs. The aim of the review is to emphasize the key role of the protein truncation in the pathogenic pathways of neurodegenerative diseases. A deeper understanding of the complex downstream processing of the IDPs, resulting in the generation of pathologically modified proteins might be a prerequisite for the successful therapeutic strategies of several fatal neurodegenerative diseases.
神经退行性折叠病的特征是病变修饰蛋白的异常折叠，这些蛋白是细胞内和细胞外损伤的主要成分。这些损伤与这些疾病中观察到的认知和/或运动障碍相关。神经退行性折叠病中大多数病变修饰蛋白属于被称为固有无序蛋白 (IDP) 的蛋白组。几项独立的研究表明，异常蛋白加工构成了这些疾病的关键病理特征。本综述重点关注蛋白截断作为神经退行性折叠病的共同特征，这被认为是脑 IDP 病理变形的主要驱动力。综述的目的是强调蛋白截断在神经退行性疾病发病机制中的关键作用。深入了解 IDP 的复杂下游加工过程，导致病理性修饰蛋白的产生，可能是成功治疗几种致命神经退行性疾病的先决条件。
