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[阿尔茨海默病的治疗前景]

[Perspectives of therapy of Alzheimer's disease].

作者信息

Sienkiewicz-Jarosz H, Kostowski W

机构信息

Zakładu Farmakologii i Fizjologii Układu Nerwowego IPiN w Warszawie.

出版信息

Psychiatr Pol. 2000 Jul-Aug;34(4):623-40.

PMID:11059261
Abstract

Alzheimer's disease is the most common cause of memory disruption in elderly people. The main pathogenic factor of the disease is beta-amyloid protein, which may cause toxic damage of neurones. Other suggested pathogenic factors include an inflammatory process around the senile plaques, apoptosis and necrotic death of neurones, and, in consequence, changes in functioning of neurotransmitter systems. In this article the authors present the main directions in pharmacotherapy of Alzheimer's disease: causal therapy, which prevents the neurodegenerative changes and slows down the pathogenetic process, and symptomatic therapy. The aim of symptomatic therapy is to reduce memory disruption and psychiatric symptoms associated with the disease. Positive influence on cognitive processes is exerted by cholinergic drugs, e.g. the actually used inhibitors of acetylcholinesterase (rivastigmine, donepezil), the nootropic agents (piracetam, nefiracetam) and extracts of Gingko biloba. For treatment of the disease accompanying psychiatric symptoms (anxiety, depression, hallucinations, sleepness) the drugs with minimal influence on cognitive processes are recommended. Attempts at causal therapy are focussed on searching for the substances that can prevent the formation and toxicity of beta-amyloid (droloksifen, estrogens, agonists of muscarinic receptors M1), the cytotoxic influence of excitatory aminoacids (memantine, lamotrigine), calcium (nimodipine) and free radicals (selegiline, alpha-tocoferol), and the development of inflammatory process (non-steroidal antiinflammatory drugs). The new target of research is correction of deficits of nerve growth factor and neurotransmitters by intracerebral implantation of modified fibroblasts. Another way is prevention of the formation of amyloid plaques using appropriate antisense oligonucleotides.

摘要

阿尔茨海默病是老年人记忆障碍最常见的病因。该病的主要致病因素是β-淀粉样蛋白,它可能导致神经元的毒性损伤。其他推测的致病因素包括老年斑周围的炎症过程、神经元的凋亡和坏死性死亡,以及由此导致的神经递质系统功能改变。在本文中,作者介绍了阿尔茨海默病药物治疗的主要方向:病因治疗,即预防神经退行性变并减缓致病过程,以及对症治疗。对症治疗的目的是减少与该病相关的记忆障碍和精神症状。胆碱能药物,如目前使用的乙酰胆碱酯酶抑制剂(卡巴拉汀、多奈哌齐)、促智药(吡拉西坦、奈非西坦)和银杏叶提取物,对认知过程有积极影响。对于伴有精神症状(焦虑、抑郁、幻觉、失眠)的疾病治疗,推荐使用对认知过程影响最小的药物。病因治疗的尝试集中在寻找能够预防β-淀粉样蛋白的形成和毒性的物质(屈洛克西芬、雌激素、M1毒蕈碱受体激动剂)、兴奋性氨基酸的细胞毒性影响(美金刚、拉莫三嗪)、钙(尼莫地平)和自由基(司来吉兰、α-生育酚),以及炎症过程的发展(非甾体抗炎药)。研究的新靶点是通过脑内植入修饰的成纤维细胞来纠正神经生长因子和神经递质的缺乏。另一种方法是使用合适的反义寡核苷酸预防淀粉样斑块的形成。

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