Marchetti Carla
Istituto di Biofisica, Consiglio Nazionale delle Ricerche, via De Marini, 6, 16149, Genoa, Italy,
Biometals. 2014 Dec;27(6):1097-113. doi: 10.1007/s10534-014-9791-y. Epub 2014 Sep 16.
There is increasing evidence that toxic metals play a role in diseases of unknown etiology. Their action is often mediated by membrane proteins, and in particular neurotransmitter receptors. This brief review will describe recent findings on the direct interaction of metal ions with ionotropic γ-aminobutyric acid (GABAA) and glutamate receptors, the main inhibitory and excitatory neurotransmitter receptors in the mammalian central nervous system, respectively. Both hyper and hypo function of these receptors are involved in neurological and psychotic syndromes and modulation by metal ions is an important pharmacological issue. The focus will be on three xenobiotic metals, lead (Pb), cadmium (Cd) and nickel (Ni) that have no biological function and whose presence in living organisms is only detrimental, and two trace metals, zinc (Zn) and copper (Cu), which are essential for several enzymatic functions, but can mediate toxic actions if deregulated. Despite limited access to the brain and tight control by metalloproteins, exogenous metals interfere with receptor performances by mimicking physiological ions and occupying one or more modulatory sites on the protein. These interactions will be discussed as a potential cause of neuronal dysfunction.
越来越多的证据表明，有毒金属在病因不明的疾病中起作用。它们的作用通常由膜蛋白介导，尤其是神经递质受体。本简要综述将描述金属离子与离子型γ-氨基丁酸（GABAA）和谷氨酸受体直接相互作用的最新发现，这两种受体分别是哺乳动物中枢神经系统主要的抑制性和兴奋性神经递质受体。这些受体的功能亢进和功能减退均与神经和精神综合征有关，金属离子对其的调节是一个重要的药理学问题。重点将放在三种无生物学功能、在生物体内的存在只会造成损害的外源性金属，即铅（Pb）、镉（Cd）和镍（Ni），以及两种对多种酶功能必不可少但如果失调会介导毒性作用的痕量金属，即锌（Zn）和铜（Cu）。尽管进入大脑的途径有限且受到金属蛋白的严格控制，但外源性金属通过模拟生理离子并占据蛋白质上的一个或多个调节位点来干扰受体性能。这些相互作用将作为神经元功能障碍的潜在原因进行讨论。
