Caminati Gabriella, Procacci Piero
Department of Chemistry "Ugo Schiff ", University of Florence; Center for Colloid and Surface Science (CSGI), University of Florence, Sesto Fiorentino, Italy.
Department of Chemistry "Ugo Schiff ", University of Florence, Sesto Fiorentino, Italy.
Neural Regen Res. 2020 Dec;15(12):2195-2202. doi: 10.4103/1673-5374.284980.
Intrinsically disordered proteins, such as tau or α-synuclein, have long been associated with a dysfunctional role in neurodegenerative diseases. In Alzheimer's and Parkinson's' diseases, these proteins, sharing a common chemical-physical pattern with alternating hydrophobic and hydrophilic domains rich in prolines, abnormally aggregate in tangles in the brain leading to progressive loss of neurons. In this review, we present an overview linking the studies on the implication of the peptidyl-prolyl isomerase domain of immunophilins, and notably FKBP12, to a variety of neurodegenerative diseases, focusing on the molecular origin of such a role. The involvement of FKBP12 dysregulation in the aberrant aggregation of disordered proteins pinpoints this protein as a possible therapeutic target and, at the same time, as a predictive biomarker for early diagnosis in neurodegeneration, calling for the development of reliable, fast and cost-effective detection methods in body fluids for community-based screening campaigns.
内在无序蛋白，如tau蛋白或α-突触核蛋白，长期以来一直被认为在神经退行性疾病中发挥着功能失调的作用。在阿尔茨海默病和帕金森病中，这些蛋白具有共同的化学物理模式，富含脯氨酸的疏水和亲水结构域交替出现，在大脑中异常聚集形成缠结，导致神经元逐渐丧失。在这篇综述中，我们概述了将亲免素的肽基脯氨酰异构酶结构域，尤其是FKBP12的相关研究与多种神经退行性疾病联系起来的研究，重点关注这种作用的分子起源。FKBP12失调参与无序蛋白的异常聚集，这表明该蛋白可能是一个治疗靶点，同时也是神经退行性疾病早期诊断的预测生物标志物，这就需要开发可靠、快速且经济高效的体液检测方法用于社区筛查活动。
