期刊
NEURODEGENERATIVE DISEASES
卷 7, 期 1-3, 页码 32-37出版社
KARGER
DOI: 10.1159/000266476
关键词
Alzheimer's disease; A beta peptides; Amyloid precursor protein; Neuronal loss
资金
- Alzheimer's Association [IIRG-06-26751]
- NATIONAL INSTITUTE ON AGING [R37AG017926] Funding Source: NIH RePORTER
Alzheimer's disease (AD) is characterized by neurodegeneration in neocortical regions of the brain. Currently, A beta-based theories, including amyloid depositions and soluble A beta, form the basis of most therapeutic approaches to AD. It remains unclear, however, whether A beta and its derivatives are the primary causative agents of neuronal loss in AD. Reported studies show no significant correlations between brain amyloid depositions and either degree of dementia or loss of neurons, and brain amyloid loads similar to AD are often found in normal individuals. Furthermore, behavioral abnormalities in animal models overexpressing amyloid precursor protein seem independent of amyloid depositions. Soluble A beta theories propose toxic A beta 42 or its oligomers as the agents that promote cell death in AD. A beta peptides, however, are normal components of human serum and CSF, and it is unclear under what conditions these peptides become toxic. Presently, there is little evidence of disease-associated abnormalities in soluble A beta and no toxic oligomers specific to AD have been found. That familial AD mutations of amyloid precursor protein, PS1 and PS2 promote neurodegeneration suggests the biological functions of these proteins play critical roles in neuronal survival. Evidence shows that the PS/gamma-secretase system promotes production of peptides involved in cell surface-to-nucleus signaling and gene expression, providing support for the hypothesis that familial AD mutations may contribute to neurodegeneration by inhibiting PS-dependent signaling pathways. Copyright (C) 2010 S. Karger AG, Basel
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据