Role of melatonin in Alzheimer-like neurodegeneration
Role of melatonin in Alzheimer-like neurodegeneration
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DOI：
10.1111/j.1745-7254.2006.00260.x
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发表时间：
2006
影响因子：
8.2
通讯作者：
Jian-Zhi Wang;Ze-Fen Wang
中科院分区：
文献类型：
--
作者：
Jian-Zhi Wang;Ze-Fen Wang
阿尔茨海默病（Alzheimer disease，AD）是一种以细胞外β-淀粉样蛋白（β-amyloid，Aβ）聚集的老年斑和细胞内tau蛋白过度磷酸化的神经元缠结为特征的进行性记忆减退和综合认知功能减退的神经退行性疾病。近年来的研究表明，松果体分泌的一种吲哚胺--褪黑激素可能作为一种抗氧化剂和神经保护剂在衰老和AD中发挥重要作用。褪黑激素在衰老过程中减少，AD患者的褪黑激素减少更严重。来自临床试验的数据表明，褪黑激素补充剂改善睡眠，改善日落，并减缓阿尔茨海默氏症患者认知障碍的进展。褪黑激素通过抗氧化和抗淀粉样蛋白特性有效保护神经元细胞免受Aβ介导的毒性：它不仅抑制Aβ生成，而且通过与Aβ的结构依赖性相互作用阻止淀粉样蛋白原纤维的形成。我们最近的研究表明，褪黑激素有效地减弱阿尔茨海默病样tau蛋白过度磷酸化。虽然确切的机制还没有完全理解，褪黑激素对蛋白激酶和蛋白磷酸酶的活性的直接调节影响。此外，褪黑激素还在保护胆碱能神经元和抗炎中起作用。在这里，褪黑激素的神经保护作用及其发挥作用的机制进行了审查。褪黑激素预防或改善tau和Aβ病理的能力进一步增强了其预防或治疗AD的潜力。
AbstractAlzheimer disease (AD), an age-related neurodegenerative disorder with progressive loss of memory and deterioration of comprehensive cognition, is characterized by extracellular senile plaques of aggregated β-amyloid (Aβ), and intracellular neurofibrillary tangles that contain hyperphosphorylated tau protein. Recent studies showed that melatonin, an indoleamine secreted by the pineal gland, may play an important role in aging and AD as an antioxidant and neuroprotector. Melatonin decreases during aging and patients with AD have a more profound reduction in this hormone. Data from clinical trials indicate that melatonin supplementation improves sleep, ameliorates sundowning, and slows down the progression of cognitive impairment in Alzheimer's patients. Melatonin efficiently protects neuronal cells from Aβ-mediated toxicity via antioxidant and anti-amyloid properties: it not only inhibits Aβ generation, but also arrests the formation of amyloid fibrils by a structure-dependent interaction with Aβ. Our recent studies have demonstrated that melatonin efficiently attenuates Alzheimer-like tau hyperphosphorylation. Although the exact mechanism is still not fully understood, a direct regulatory influence of melatonin on the activities of protein kinases and protein phosphatases is proposed. Additionally, melatonin also plays a role in protecting cholinergic neurons and in anti-inflammation. Here, the neuroprotective effects of melatonin and the underlying mechanisms by which it exerts its effects are reviewed. The capacity of melatonin to prevent or ameliorate tau and Aβ pathology further enhances its potential in the prevention or treatment of AD.