Menini Teresita, Gugliucci Alejandro
Redox Rep. 2014 Mar;19(2):49-58. doi: 10.1179/1351000213Y.0000000071. Epub 2013 Nov 12.
Paroxonase 1 displays multiple physiological activities that position it as a putative player in the pathogenesis of neurological disorders. Here we reviewed the literature focusing on the role of paraoxonase 1 (PON1) as a factor in the risk of stroke and the major neurodegenerative diseases. PON1 activity is reduced in stroke patients, which significantly correlates inversely with carotid and cerebral atherosclerosis. The presence of the R allele of the Q192R PON1 polymorphism seems to potentiate this risk for stroke. PON1 exerts peroxidase activities that may be important in neurodegenerative disorders associated with oxidative stress. PON1 is also a key detoxifier of organophosphates and organophosphate exposure has been linked to the development of neurological disorders in which acetylcholine plays a significant role. In Parkinson's disease most of the studies suggest no participation of either L55M or the Q192R polymorphisms in its pathogenesis. However, many studies suggest that the MM55 PON1 genotype is associated with a higher risk for Parkinson's disease in individuals exposed to organophosphates. In Alzheimer's disease most studies have failed to find any association between PON1 polymorphisms and the development of the disease. Some studies show that PON1 activity is decreased in patients with Alzheimer's disease or other dementias, suggesting a possible protective role of PON1. No links between PON1 polymorphisms or activity have been found in other neurodegenerative diseases such as multiple sclerosis and amyotrophic lateral sclerosis. PON1 is a potential player in the pathogenesis of several neurological disorders. More research is warranted to ascertain the precise pathogenic links and the prognostic value of its measurement in neurological patients.
对氧磷酶1具有多种生理活性，使其成为神经疾病发病机制中的一个潜在因素。在此，我们回顾了相关文献，重点关注对氧磷酶1（PON1）作为中风和主要神经退行性疾病风险因素的作用。中风患者的PON1活性降低，这与颈动脉和脑动脉粥样硬化显著负相关。Q192R PON1多态性的R等位基因的存在似乎会增加中风风险。PON1具有过氧化物酶活性，这在与氧化应激相关的神经退行性疾病中可能很重要。PON1也是有机磷酸酯的关键解毒剂，有机磷酸酯暴露与神经疾病的发生有关，其中乙酰胆碱起重要作用。在帕金森病中，大多数研究表明L55M或Q192R多态性在其发病机制中不起作用。然而，许多研究表明，MM55 PON1基因型与接触有机磷酸酯的个体患帕金森病的风险较高有关。在阿尔茨海默病中，大多数研究未能发现PON1多态性与疾病发生之间的任何关联。一些研究表明，阿尔茨海默病或其他痴呆症患者的PON1活性降低，提示PON1可能具有保护作用。在其他神经退行性疾病如多发性硬化症和肌萎缩侧索硬化症中，未发现PON1多态性或活性之间的联系。PON1是几种神经疾病发病机制中的一个潜在因素。有必要进行更多研究以确定其确切的致病联系及其在神经疾病患者中的测量的预后价值。
