Strømland Øyvind, Jakubec Martin, Furse Samuel, Halskau Øyvind
Department of Molecular Biology, University of Bergen, Bergen, Norway.
J Clin Transl Res. 2016 Mar 22;2(1):11-26. eCollection 2016 Apr 15.
Neurodegenerative Protein Misfolding Diseases (PMDs), such as Alzheimer's (AD), Parkinson's (PD) and prion diseases, are generally difficult to diagnose before irreversible damage to the central nervous system damage has occurred. Detection of the misfolded proteins that ultimately lead to these conditions offers a means for providing early detection and diagnosis of this class of disease. In this review, we discuss recent developments surrounding protein misfolding diseases with emphasis on the cytotoxic oligomers implicated in their aetiology. We also discuss the relationship of misfolded proteins with biological membranes. Finally, we discuss how far techniques for providing early diagnoses for PMDs have advanced and describe promising clinical approaches. We conclude that antibodies with specificity towards oligomeric species of AD and PD and lectins with specificity for particular glycosylation, show promise. However, it is not clear which approach may yield a reliable clinical test first. Individuals suffering from protein misfolding diseases will likely benefit form earlier, less- or even non-invasive diagnosis techniques. The current state and possible future directions for these are subject of this review.
神经退行性蛋白质错误折叠疾病（PMD），如阿尔茨海默病（AD）、帕金森病（PD）和朊病毒病，通常在中枢神经系统发生不可逆损伤之前很难诊断。检测最终导致这些疾病的错误折叠蛋白为这类疾病的早期检测和诊断提供了一种方法。在这篇综述中，我们讨论了围绕蛋白质错误折叠疾病的最新进展，重点是涉及其病因的细胞毒性寡聚体。我们还讨论了错误折叠蛋白与生物膜的关系。最后，我们讨论了为PMD提供早期诊断的技术进展程度，并描述了有前景的临床方法。我们得出结论，对AD和PD的寡聚体具有特异性的抗体以及对特定糖基化具有特异性的凝集素显示出前景。然而，尚不清楚哪种方法可能首先产生可靠的临床检测。患有蛋白质错误折叠疾病的个体可能会从更早、更少甚至非侵入性的诊断技术中受益。这些技术的当前状态和可能的未来方向是本综述的主题。
