Recent studies highlight the initiation of Parkinson's disease (PD) in the gastrointestinal tract, decades before the manifestations in the central nervous system (CNS). This gut-brain axis of neurodegenerative diseases defines the critical role played by the unique microbial composition of the "second brain" formed by the enteric nervous system (ENS). Compromise in the enteric wall can result in the translocation of gut-microbiota along with their metabolites into the system that can affect the homeostatic machinery. The released metabolites can associate with protein substrates affecting several biological pathways. Among these, the bacterial endotoxin from Gram-negative bacteria, i.e., Lipopolysaccharide (LPS), has been implicated to play a definite role in progressive neurodegeneration. The molecular interaction of the lipid metabolites can have a direct neuro-modulatory effect on homeostatic protein components that can be transported to the CNS via the vagus nerve. α-synuclein (α-syn) is one such partner protein, the molecular interactions with which modulate its overall fibrillation propensity in the system. LPS interaction has been shown to affect the protein's aggregation kinetics in an alternative inflammatory pathway of PD pathogenesis. Several other lipid contents from the bacterial membranes could also be responsible for the initiation of α-syn amyloidogenesis. The present review will focus on the intermolecular interactions of α-syn with bacterial lipid components, particularly LPS, with a definite clinical manifestation in PD pathogenesis. However, deconvolution of the sequence of interaction events from the ENS to its propagation in the CNS is not easy or obvious. Nevertheless, the characterization of these lipid-mediated structures is a step towards realizing the novel targets in the pre-emptive diagnoses of PD. This comprehensive description should prompt the correlation of potential risk of amyloidogenesis upon detection of specific paradigm shifts in the microbial composition of the gut.

最近的研究强调了帕金森病 (PD) 在胃肠道中的开始，比中枢神经系统 (CNS) 的表现早几十年。神经退行性疾病的这种肠脑轴定义了由肠神经系统 (ENS) 形成的“第二大脑”的独特微生物组成所发挥的关键作用。肠壁受损会导致肠道微生物群及其代谢物转移到系统中，从而影响体内平衡机制。释放的代谢物可以与影响几种生物途径的蛋白质底物相关联。其中，革兰氏阴性菌的细菌内毒素，即脂多糖 (LPS) 已被认为在进行性神经退行性疾病中发挥了明确的作用。脂质代谢物的分子相互作用可以对稳态蛋白质成分产生直接的神经调节作用，这些成分可以通过迷走神经。α-突触核蛋白 (α-syn) 是一种这样的伴侣蛋白，分子相互作用调节其在系统中的整体纤维化倾向。LPS 相互作用已被证明会影响蛋白质在 PD 发病机制的另一种炎症途径中的聚集动力学。来自细菌膜的其他几种脂质成分也可能是 α-syn 淀粉样蛋白生成的原因。本综述将重点关注 α-syn 与细菌脂质成分，特别是 LPS 的分子间相互作用，在 PD 发病机制中具有明确的临床表现。然而，从 ENS 到其在 CNS 中传播的交互事件序列的去卷积并不容易或明显。尽管如此，这些脂质介导的结构的表征是朝着在 PD 的先发制人诊断中实现新目标迈出的一步。这种全面的描述应该会在检测到肠道微生物组成的特定范式转变时提示淀粉样蛋白生成的潜在风险之间的相关性。