Department of Physiology, Universidad de Concepción, Concepción 4070386, Chile.
Centro de Medicina Regenerativa, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Santiago 7710162, Chile.
Cells. 2020 Nov 13;9(11):2476. doi: 10.3390/cells9112476.
Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) and Creutzfeldt-Jakob disease (CJD) are brain conditions affecting millions of people worldwide. These diseases are associated with the presence of amyloid-β (Aβ), alpha synuclein (α-Syn) and prion protein (PrP) depositions in the brain, respectively, which lead to synaptic disconnection and subsequent progressive neuronal death. Although considerable progress has been made in elucidating the pathogenesis of these diseases, the specific mechanisms of their origins remain largely unknown. A body of research suggests a potential association between host microbiota, neuroinflammation and dementia, either directly due to bacterial brain invasion because of barrier leakage and production of toxins and inflammation, or indirectly by modulating the immune response. In the present review, we focus on the emerging topics of neuroinflammation and the association between components of the human microbiota and the deposition of Aβ, α-Syn and PrP in the brain. Special focus is given to gut and oral bacteria and biofilms and to the potential mechanisms associating microbiome dysbiosis and toxin production with neurodegeneration. The roles of neuroinflammation, protein misfolding and cellular mediators in membrane damage and increased permeability are also discussed.
神经退行性疾病，如阿尔茨海默病（AD）、帕金森病（PD）和克雅氏病（CJD），是影响全球数百万人的脑部疾病。这些疾病分别与脑内淀粉样蛋白-β（Aβ）、α-突触核蛋白（α-Syn）和朊病毒蛋白（PrP）沉积有关，导致突触断开和随后的进行性神经元死亡。尽管在阐明这些疾病的发病机制方面已经取得了相当大的进展，但它们起源的确切机制在很大程度上仍不清楚。大量研究表明，宿主微生物群、神经炎症与痴呆之间存在潜在关联，其原因可能直接是由于屏障渗漏和毒素及炎症的产生导致细菌侵入大脑，也可能间接通过调节免疫反应。在本综述中，我们重点关注神经炎症的新出现主题，以及人类微生物群的组成部分与脑内 Aβ、α-Syn 和 PrP 沉积之间的关联。特别关注肠道和口腔细菌和生物膜，以及与微生物组失调和毒素产生相关的潜在机制与神经退行性变的关联。还讨论了神经炎症、蛋白质错误折叠和细胞介质在膜损伤和通透性增加中的作用。
