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神经营养因子:从阿尔茨海默病的病理生理学到治疗

Neurotrophins: from pathophysiology to treatment in Alzheimer's disease.

作者信息

Schulte-Herbrüggen Olaf, Jockers-Scherübl Maria C, Hellweg Rainer

机构信息

Department of Psychiatry and Psychotherapy, Charité University Medicine Berlin, Campus Benjamin Franklin, Humboldt University and Free University of Berlin, Germany.

出版信息

Curr Alzheimer Res. 2008 Feb;5(1):38-44. doi: 10.2174/156720508783884620.

Abstract

Alzheimer's disease (AD) is the most common diagnosis among dementia. As increasing longevity results in larger numbers of AD patients and thus rising economic costs, there has been intense research about the pathophysiology and treatment strategies during the last years. Since neurotrophic factors are not only responsible for neuronal development but also critical for the maintenance of neurons, they represent mediators of high interest within the research of neurodegeneration. Thereby, NGF has been identified as a dynamic pattern during the time course of neurodegeneration in AD. Post mortem studies point to a lack of NGF action in early stages of AD. In contrast NGF is found in enhanced concentrations in brains with severe AD partly due to a pathologically altered axonal transport of NGF in the neurons. Therefore, pharmacological interventions strategies focus on an neurotrophin substitution in mild to moderate cases of AD. Intensive research mostly in rodents has recently led to first promising clinical trials of intracerebral neurotrophin application pointing to a growing role of neurotrophins in the establishment of new pharmacological strategies concerning AD.

摘要

阿尔茨海默病(AD)是痴呆症中最常见的诊断类型。随着寿命延长导致AD患者数量增加,进而使经济成本上升,在过去几年中,人们对其病理生理学和治疗策略进行了深入研究。由于神经营养因子不仅负责神经元发育,而且对神经元的维持至关重要,它们在神经退行性变研究中是备受关注的介质。因此,NGF已被确定为AD神经退行性变过程中的一种动态模式。尸检研究表明,AD早期缺乏NGF作用。相反,在重度AD患者的大脑中发现NGF浓度升高,部分原因是神经元中NGF的轴突运输发生了病理性改变。因此,药物干预策略集中在轻度至中度AD病例的神经营养因子替代上。最近主要在啮齿动物身上进行的深入研究已导致首次进行脑内应用神经营养因子的有前景的临床试验,这表明神经营养因子在建立有关AD的新药理学策略中发挥着越来越重要的作用。

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