St. Petersburg State University, Institute of Chemistry, St. Petersburg, Russian Federation.
Universität Potsdam, Institut für Ernährungswissenschaft, Potsdam, Germany.
Free Radic Biol Med. 2018 Nov 1;127:124-133. doi: 10.1016/j.freeradbiomed.2018.02.030. Epub 2018 Mar 2.
The essential trace element, selenium (Se), is crucial to the brain but it may be potentially neurotoxic, depending on dosage and speciation; Se has been discussed for decades in relation to Alzheimer's disease (AD). Selenoprotein P (SELENOP) is a secreted heparin-binding glycoprotein which serves as the main Se transport protein in mammals. In vivo studies showed that this protein might have additional functions such as a contribution to redox regulation. The current review focuses on recent research on the possible role of SELENOP in AD pathology, based on model and human studies. The review also briefly summarizes results of epidemiological studies on Se supplementation in relation to brain diseases, including PREADViSE, EVA, and AIBL. Although mainly positive effects of Se are assessed in this review, possible detrimental effects of Se supplementation or exposure, including potential neurotoxicity, are also mentioned. In relation to AD, various roles of SELENOP are discussed, i.e. as the means of Se delivery to neurons, as an antioxidant, in cytoskeleton assembly, in interaction with redox-active metals (copper, iron, and mercury) and with misfolded proteins (amyloid-beta and hyperphosphorylated tau-protein).
必需微量元素硒 (Se) 对大脑至关重要，但它可能具有潜在的神经毒性，具体取决于剂量和形态；几十年来，人们一直在讨论硒与阿尔茨海默病 (AD) 的关系。硒蛋白 P (SELENOP) 是一种分泌的肝素结合糖蛋白，是哺乳动物中主要的 Se 转运蛋白。体内研究表明，这种蛋白质可能具有其他功能，例如有助于氧化还原调节。本综述基于模型和人类研究，重点介绍了最近关于 SELENOP 在 AD 病理中的可能作用的研究。该综述还简要总结了与脑部疾病相关的硒补充的流行病学研究结果，包括 PREADViSE、EVA 和 AIBL。尽管本综述主要评估了硒的积极作用，但也提到了硒补充或暴露的潜在有害影响，包括潜在的神经毒性。在与 AD 相关的方面，讨论了 SELENOP 的各种作用，即作为将 Se 递送到神经元的手段、作为抗氧化剂、在细胞骨架组装中的作用、与氧化还原活性金属（铜、铁和汞）以及与错误折叠蛋白（淀粉样β和过度磷酸化的 tau 蛋白）的相互作用。
