Marcelli Serena, Corbo Massimo, Iannuzzi Filomena, Negri Lucia, Blandini Fabio, Nistico Robert, Feligioni Marco
Laboratory of Pharmacology of Synaptic Disease, EBRI Rita Levi-Montalcini Foundation, Rome, Italy.
Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
Curr Alzheimer Res. 2018 Feb 22;15(4):313-335. doi: 10.2174/1567205014666170505095109.
Alzheimer's disease (AD) is a neurodegenerative disorder recognized as the most common cause of chronic dementia among the ageing population. AD is histopathologically characterized by progressive loss of neurons and deposits of insoluble proteins, primarily composed of amyloid-β pelaques and neurofibrillary tangles (NFTs).
Several molecular processes contribute to the formation of AD cellular hallmarks. Among them, post-translational modifications (PTMs) represent an attractive mechanism underlying the formation of covalent bonds between chemical groups/peptides to target proteins, which ultimately result modified in their function. Most of the proteins related to AD undergo PTMs. Several recent studies show that AD-related proteins like APP, Aβ, tau, BACE1 undergo post-translational modifications. The effect of PTMs contributes to the normal function of cells, although aberrant protein modification, which may depend on many factors, can drive the onset or support the development of AD.
Here we will discuss the effect of several PTMs on the functionality of AD-related proteins potentially contributing to the development of AD pathology.
We will consider the role of Ubiquitination, Phosphorylation, SUMOylation, Acetylation and Nitrosylation on specific AD-related proteins and, more interestingly, the possible interactions that may occur between such different PTMs.
阿尔茨海默病（AD）是一种神经退行性疾病，被认为是老年人群中慢性痴呆最常见的病因。AD的组织病理学特征是神经元逐渐丧失以及不溶性蛋白质沉积，主要由β-淀粉样蛋白斑块和神经原纤维缠结（NFTs）组成。
多种分子过程促成了AD细胞特征的形成。其中，翻译后修饰（PTM）是一种有吸引力的机制，它是化学基团/肽与靶蛋白之间形成共价键的基础，最终导致其功能发生改变。大多数与AD相关的蛋白质都会经历PTM。最近的几项研究表明，与AD相关的蛋白质，如APP、Aβ、tau、BACE1都会发生翻译后修饰。PTM的作用有助于细胞的正常功能，尽管异常的蛋白质修饰（可能取决于多种因素）会引发AD的发病或促进其发展。
在这里，我们将讨论几种PTM对AD相关蛋白质功能的影响，这些影响可能促成AD病理学的发展。
我们将考虑泛素化、磷酸化、SUMO化、乙酰化和亚硝基化对特定AD相关蛋白质的作用，更有趣的是，考虑这些不同PTM之间可能发生的相互作用。
