The toxicology of aluminum in the brain: a review.
The toxicology of aluminum in the brain: a review.
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作者：
R. Yokel
铝在环境中无处不在，提供人类暴露。人体接触主要是饮食。应进一步研究从鼻腔显著吸收铝并直接分布到大脑中的可能性。肾功能下降会增加铝诱导蓄积和毒性的人体风险。从血液进入脑铝可能涉及转铁蛋白受体介导的内吞作用和更快速的过程中运输小分子量铝物种。似乎有铝从大脑流出，可能是柠檬酸铝。有一部分进入大脑的铝的长期保留，这表明重复暴露的积累潜力。铝是动物和人类的神经毒物。它与散发性阿尔茨海默病（AD）和其他神经退行性疾病的病因有关，尽管这是非常有争议的。流行病学研究尚未解决这一争议，因为只有一些研究发现痴呆症发病率增加与饮用水铝浓度之间存在微小关联。对AD患者脑铝的研究没有得出一致的结果，也没有解决争议。向动物注射Al产生部分模拟AD的行为、神经病理学和神经化学变化。铝具有通过多种机制产生神经毒性的能力。过量的不溶性淀粉样β蛋白（A β）有助于AD。铝促进不溶性A β和过度磷酸化tau蛋白的形成和积累。在某种程度上，铝模拟了AD中所见的皮质胆碱能神经传递的缺陷。铝增加铁诱导的氧化损伤。铝对植物、水生生物和人类的毒性机制可能有共同之处，包括破坏磷酸肌醇系统和钙调节。铁诱导的氧化损伤和基本细胞过程的破坏的促进可能介导铝诱导的神经毒性的主要分子机制。在可行的情况下，避免铝暴露似乎是谨慎的。
Aluminum is environmentally ubiquitous, providing human exposure. Usual human exposure is primarily dietary. The potential for significant Al absorption from the nasal cavity and direct distribution into the brain should be further investigated. Decreased renal function increases human risk of Al-induced accumulation and toxicity. Brain Al entry from blood may involve transferrin-receptor mediated endocytosis and a more rapid process transporting small molecular weight Al species. There appears to be Al efflux from the brain, probably as Al citrate. There is prolonged retention of a fraction of Al that enters the brain, suggesting the potential for accumulation with repeated exposure. Al is a neurotoxicant in animals and humans. It has been implicated in the etiology of sporadic Alzheimer's disease (AD) and other neurodegenerative disorders, although this is highly controversial. This controversy has not been resolved by epidemiological studies, as only some found a small association between increased incidence of dementia and drinking water Al concentration. Studies of brain Al in AD have not produced consistent findings and have not resolved the controversy. Injections of Al to animals produce behavioral, neuropathological and neurochemical changes that partially model AD. Aluminum has the ability to produce neurotoxicity by many mechanisms. Excess, insoluble amyloid beta protein (A beta) contributes to AD. Aluminum promotes formation and accumulation of insoluble A beta and hyperphosphorylated tau. To some extent, Al mimics the deficit of cortical cholinergic neurotransmission seen in AD. Al increases Fe-induced oxidative injury. The toxicity of Al to plants, aquatic life and humans may share common mechanisms, including disruption of the inositol phosphate system and Ca regulation. Facilitation of Fe-induced oxidative injury and disruption of basic cell processes may mediate primary molecular mechanisms of Al-induced neurotoxicity. Avoidance of Al exposure, when practical, seems prudent.