阿尔茨海默病中神经保护和神经元素

Neurodegeneration in Alzheimer’s disease (AD) is thought to be initiated by a cascade of neurotoxic events that include oxidative stress, brain iron dysregulation, glutamate excitotoxicity, nitric oxide, inflammatory process, neurotoxic processing resulting from misfolding, and aggregation of Abeta peptide, as a possible consequence of the demise of ubiquitin-proteasome system (UPS) which is demonstrated neurochemically and by transcriptomics and proteomic profiling. AD is benefitted from the symptomatic effects of cholinesterase inhibitors and glutamate antagonist (memantine), which act on a single molecular target. Such drugs have limited symptomatic activities, and current pharmacological approaches have severe limitations in their ability to be neuroprotective and to modify the course of the disease, offering incomplete and transient benefit to patients. Yet in laboratory and animal models, a number of drugs have demonstrated the ability to be neuroprotective, but in clinical trials, they have failed as a form of symptomatic treatment and disease modification. This situation is not different from that of Parkinson’s disease or amyotrophic lateral sclerosis, where the same problems exist. There are a number of valid reasons why we have failed to alter the course of these progressive neurodegenerative disorders. First and foremost, the models employed体外和体内在人类中，不是复杂疾病的真实表示。大多数努力一直朝着预防表达Abeta肽和斑块的转基因小鼠中的Abeta肽的形成和过表达。然而在这些动物中，没有神经变性的过程。然而，一个必须质疑这种疾病是疾病是否是肽诱导的斑块形成的疾病，导致认知下降或涉及其他过程。希望是新开发的大鼠转基因模型，其模拟广告的许多特征，将推进对疾病的病理理解，可能导致新的治疗策略的发展。AD途径的复杂病理包括基因表达，蛋白质代谢，受体响应，神经递质水平，激酶活性和信号通路的变化。神经保护和神经再生中最重要的事件是选择包括合成产品，天然产物，淀粉样蛋白合成，激素平衡和用于各种生化靶标如氧化胁迫的纳米颗粒的药物。这一特别问题提供了一种基于治疗性候选人的新知识，该候选人旨在采取涉及神经变性过程中涉及的多种神经和生化目标，并具有神经保护和神经医生活动。

金滨苏格达亚
Moussa B. H. Youdim
Agneta Nordberg.
K. S. Jagannatha Rao

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