Mechanisms of Alzheimer's Disease Pathogenesis and Prevention: The Brain, Neural Pathology, N-methyl-D-aspartate Receptors, Tau Protein and Other Risk Factors.
Mechanisms of Alzheimer's Disease Pathogenesis and Prevention: The Brain, Neural Pathology, N-methyl-D-aspartate Receptors, Tau Protein and Other Risk Factors.
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DOI：
10.9758/cpn.2017.15.1.1
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发表时间：
2017-02-28
期刊：
影响因子：
--
通讯作者：
Doğan Z
中科院分区：
文献类型：
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作者：
Kocahan S;Doğan Z
阿尔茨海默病 (AD) 的特征是细胞外淀粉样蛋白 (Aβ) 斑块的出现和细胞内环境中的神经原纤维缠结、神经元死亡和突触丧失，所有这些都会导致认知能力逐渐下降。人们提出了许多假设来解释AD。 tau 磷酸化异常可能导致异常神经原纤维结构的形成。许多不同的结构都容易受到 AD 的影响，包括网状结构、脑干中的核（例如中缝核）、丘脑、下丘脑、蓝斑、杏仁核、黑质、纹状体和屏状体。兴奋性毒性是由 N-甲基-D-天冬氨酸 (NMDA) 受体持续、低水平激活引起的。过早的突触毒性、神经递质表达的变化、神经细胞损失、β-淀粉样蛋白沉积物（淀粉样蛋白/老年斑）的积累以及神经元损失和脑萎缩都与 AD 进展阶段相关。最近的几项研究探讨了 Aβ 和 NMDA 受体之间的关系。 Aβ 诱导的脊柱损失与谷氨酸受体的减少有关，并且依赖于钙依赖性磷酸酶钙调神经磷酸酶，这也与长期抑郁症有关。
The characteristic features of Alzheimer’s disease (AD) are the appearance of extracellular amyloid-beta (Aβ) plaques and neurofibrillary tangles in the intracellular environment, neuronal death and the loss of synapses, all of which contribute to cognitive decline in a progressive manner. A number of hypotheses have been advanced to explain AD. Abnormal tau phosphorylation may contribute to the formation of abnormal neurofibrillary structures. Many different structures are susceptible to AD, including the reticular formation, the nuclei in the brain stem (e.g., raphe nucleus), thalamus, hypothalamus, locus ceruleus, amygdala, substantia nigra, striatum, and claustrum. Excitotoxicity results from continuous, low-level activation of N-methyl-D-aspartate (NMDA) receptors. Premature synaptotoxicity, changes in neurotransmitter expression, neurophils loss, accumulation of amyloid β-protein deposits (amyloid/senile plaques), and neuronal loss and brain atrophy are all associated with stages of AD progression. Several recent studies have examined the relationship between Aβ and NMDA receptors. Aβ-induced spine loss is associated with a decrease in glutamate receptors and is dependent upon the calcium-dependent phosphatase calcineurin, which has also been linked to long-term depression.