Gene therapy in Alzheimer's disease - potential for disease modification.
Gene therapy in Alzheimer's disease - potential for disease modification.
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DOI：
10.1111/j.1582-4934.2010.01038.x
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发表时间：
2010-04
影响因子：
5.3
通讯作者：
Saido TC
中科院分区：
文献类型：
--
作者：
Nilsson P;Iwata N;Muramatsu S;Tjernberg LO;Winblad B;Saido TC
阿尔茨海默病（AD）是老年人痴呆的主要病因，导致记忆力丧失和认知能力下降。该病发病的潜在机制尚未完全阐明。然而，其特征性病理表现包括淀粉样β肽（Aβ）在细胞外积聚并聚集成斑块，以及过度磷酸化的tau蛋白在细胞内积聚并聚集成神经原纤维缠结。尽管全球进行了广泛的研究，但目前还没有能够改变疾病进程的治疗方法。在这篇综述中，我们聚焦于基因疗法作为阿尔茨海默病的一种潜在治疗方法，并总结了该领域近期的工作，从动物模型的概念验证研究到临床试验。阿尔茨海默病的多因素病因为基因疗法提供了多种可能的靶点，包括两种神经营养生长因子，即神经生长因子和脑源性神经营养因子，Aβ降解酶，如脑啡肽酶、内皮素转化酶和组织蛋白酶B，以及与阿尔茨海默病相关的载脂蛋白E。这篇综述还讨论了用于基因疗法的各种快速发展的病毒介导的基因传递技术的优缺点。最后，简要总结了通过小干扰RNA介导的基因敲低来下调淀粉样前体蛋白（APP）和β位点APP裂解酶1水平的方法。总体而言，基因疗法有可能成为阿尔茨海默病的一种改变疾病进程的治疗方法，前景似乎充满希望。
Alzheimer’s disease (AD) is the major cause of dementia in the elderly, leading to memory loss and cognitive decline. The mechanism underlying onset of the disease has not been fully elucidated. However, characteristic pathological manifestations include extracellular accumulation and aggregation of the amyloid β-peptide (Aβ) into plaques and intracellular accumulation and aggregation of hyperphosphorylated tau, forming neurofibrillary tangles. Despite extensive research worldwide, no disease modifying treatment is yet available. In this review, we focus on gene therapy as a potential treatment for AD, and summarize recent work in the field, ranging from proof-of-concept studies in animal models to clinical trials. The multifactorial causes of AD offer a variety of possible targets for gene therapy, including two neurotrophic growth factors, nerve growth factor and brain-derived neurotrophic factor, Aβ-degrading enzymes, such as neprilysin, endothelin-converting enzyme and cathepsin B, and AD associated apolipoprotein E. This review also discusses advantages and drawbacks of various rapidly developing virus-mediated gene delivery techniques for gene therapy. Finally, approaches aiming at down-regulating amyloid precursor protein (APP) and β-site APP cleaving enzyme 1 levels by means of siRNA-mediated knockdown are briefly summarized. Overall, the prospects appear hopeful that gene therapy has the potential to be a disease modifying treatment for AD.
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影响因子：
12.4
作者：
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通讯作者：
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DOI：
10.1073/pnas.98.4.1941
发表时间：
2001-02-13
影响因子：
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作者：
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通讯作者：
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影响因子：
34.7
作者：
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通讯作者：
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DOI：
10.1016/s0169-328x(97)00125-3
发表时间：
1997-10-03
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Connor, B;Young, D;Dragunow, M
通讯作者：
Dragunow, M