Mechanisms of Molecular Mimicry Involving the Microbiota in Neurodegeneration
Mechanisms of Molecular Mimicry Involving the Microbiota in Neurodegeneration
复制标题
DOI：
10.3233/jad-142841
复制
发表时间：
2015-01-01
影响因子：
4
通讯作者：
Friedland, Robert P.
中科院分区：
文献类型：
--
作者：
Friedland, Robert P.
分子拟态的概念是为了解释在进化压力下发展起来的结构的共性而建立的。在医学中，分子模拟的大多数例子都涉及引起疾病的蛋白质一级结构的同源性。分子模拟可以扩展到氨基酸序列之外，以包括微小RNA和蛋白质组学效应，其对于帕金森病、阿尔茨海默病和相关病症是致病的或有益的。动物或植物来源的病毒可以模仿microRNA的核苷酸序列并影响蛋白质表达。帕金森病和阿尔茨海默病都涉及可传播的自我繁殖朊病毒样蛋白的形成。然而，负责创建这些错误折叠成核因子的起始因素是未知的。淀粉样蛋白折叠模式在进化过程中高度保守，并且在世界上广泛分布。三级蛋白质结构的相似性可能参与通过分子模拟产生这些朊病毒样因子。淀粉样蛋白错误折叠、蛋白质稳态改变和氧化应激的交叉接种可能是由肠道和饮食中微生物群中细菌中的淀粉样蛋白引起的。神经变性中细菌淀粉样蛋白诱导的分子模拟诱导过程的途径可能涉及TLR 2/1、CD 14和NF κ B B等。此外，通过微生物群引发先天免疫系统可增强对脑淀粉样蛋白（如淀粉样蛋白-β和α-突触核蛋白）的炎症反应。本文描述了这些交叉播种和神经炎症过程的特定分子途径。蛋白质的进化保守性为保守序列和结构提供了通过分子模拟影响神经疾病的机会。
The concept of molecular mimicry was established to explain commonalities of structure which developed in response to evolutionary pressures. Most examples of molecular mimicry in medicine have involved homologies of primary protein structure which cause disease. Molecular mimicry can be expanded beyond amino acid sequence to include microRNA and proteomic effects which are either pathogenic or salutogenic (beneficial) in regard to Parkinson's disease, Alzheimer's disease, and related disorders. Viruses of animal or plant origin may mimic nucleotide sequences of microRNAs and influence protein expression. Both Parkinson's and Alzheimer's diseases involve the formation of transmissible self-propagating prion-like proteins. However, the initiating factors responsible for creation of these misfolded nucleating factors are unknown. Amyloid patterns of protein folding are highly conserved through evolution and are widely distributed in the world. Similarities of tertiary protein structure may be involved in the creation of these prion-like agents through molecular mimicry. Cross-seeding of amyloid misfolding, altered proteostasis, and oxidative stress may be induced by amyloid proteins residing in bacteria in our microbiota in the gut and in the diet. Pathways of molecular mimicry induced processes induced by bacterial amyloid in neurodegeneration may involve TLR 2/1, CD14, and NF kappa B, among others. Furthermore, priming of the innate immune system by the microbiota may enhance the inflammatory response to cerebral amyloids (such as amyloid-beta and alpha-synuclein). This paper describes the specific molecular pathways of these cross-seeding and neuroinflammatory processes. Evolutionary conservation of proteins provides the opportunity for conserved sequences and structures to influence neurological disease through molecular mimicry.