Vegas-Suárez Sergio, Simón Jorge, Martínez-Chantar María Luz, Moratalla Rosario
Department of Pharmacology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain.
Cajal Institute, Spanish National Research Council (CSIC), Madrid, Spain.
Front Physiol. 2022 May 12;13:864263. doi: 10.3389/fphys.2022.864263. eCollection 2022.
Chronic liver diseases include a broad group of hepatic disorders from different etiologies and with varying degrees of progression and severity. Among them, non-alcoholic fatty (NAFLD) and alcoholic (ALD) liver diseases are the most frequent forms of expression, caused by either metabolic alterations or chronic alcohol consumption. The liver is the main regulator of energy homeostasis and metabolism of potentially toxic compounds in the organism, thus hepatic disorders often promote the release of harmful substances. In this context, there is an existing interconnection between liver and brain, with the well-named brain-liver axis, in which liver pathologies lead to the promotion of neurodegenerative disorders. Alzheimer's (AD) and Parkinson's (PD) diseases are the most relevant neurological disorders worldwide. The present work highlights the relevance of the liver-related promotion of these disorders. Liver-related hyperammonemia has been related to the promotion of perturbations in nervous systems, whereas the production of ketone bodies under certain conditions may protect from developing them. The capacity of the liver of amyloid- (A) clearance is reduced under liver pathologies, contributing to the development of AD. These perturbations are even aggravated by the pro-inflammatory state that often accompanies liver diseases, leading to the named neuroinflammation. The current nourishment habits, named as Western diet (WD) and alterations in the bile acid (BA) profile, whose homeostasis is controlled by the liver, have been also related to both AD and PD, whereas the supplementation with certain compounds, has been demonstrated to alleviate the pathologies.
慢性肝病包括一组病因各异、进展程度和严重程度不同的肝脏疾病。其中，非酒精性脂肪性肝病（NAFLD）和酒精性肝病（ALD）是最常见的表现形式，分别由代谢改变或长期饮酒引起。肝脏是机体能量稳态和潜在有毒化合物代谢的主要调节器官，因此肝脏疾病常促使有害物质释放。在这种情况下，肝脏与大脑之间存在一种既定的联系，即所谓的脑-肝轴，肝脏病变会导致神经退行性疾病的发生。阿尔茨海默病（AD）和帕金森病（PD）是全球最主要的神经疾病。本研究强调了肝脏相关因素在这些疾病发生中的重要性。肝脏相关的高氨血症与神经系统紊乱的发生有关，而在某些情况下酮体的产生可能对其有保护作用。肝脏病变时，肝脏清除淀粉样蛋白（A）的能力降低，这有助于AD的发展。这些紊乱甚至会因肝脏疾病常伴随的促炎状态而加剧，导致所谓的神经炎症。目前被称为西方饮食（WD）的饮食习惯以及胆汁酸（BA）谱的改变（其稳态由肝脏控制）也与AD和PD有关，而补充某些化合物已被证明可缓解这些疾病。
