期刊
IUBMB LIFE
卷 61, 期 5, 页码 516-521出版社
WILEY-BLACKWELL
DOI: 10.1002/iub.187
关键词
molecular signaling; kinase; neurodegeneration; memory
资金
- Medical Research Council
- Biological Biotechnological Sciences Research Council
- Wellcome Trust
- Alzheimer's Research Trust
- Alzheimer Society
- Medical Research Council [G0400983] Funding Source: researchfish
- MRC [G0400983] Funding Source: UKRI
Abnormalities in molecular signalling have been implicated in neurodegeneration. It is emerging that glycogen synthase kinase-3 (GSK-3) is a key signalling molecule that induces neurodegeneration and deficits in memory formation related to Alzheimer's disease (AD). Early stages of AD are associated with deficits in memory formation before neuronal cell death is detectable. Recent studies in rodents have suggested that these impairments in memory formation might result from increased GSK-3 signalling, because enhanced GSK-3 activity impairs hippocampal memory formation. GSK-3 activity blocks synaptic long-term potentiation and induces long-term depression. Furthermore, increased GSK-3 signalling is likely to be a key contributor to the formation of the pathological hallmarks in AD, neurofibrillary tangles (NFTs) and amyloid plaques. Recent studies with mouse models have indicated that GSK-3, but not cycl in-dependent kinase 5, is critical for hyperphosphorylation of the cytoskeletal protein tau, which is the prerequisite for NFT formation in AD. Furthermore, increased GSK-3 signalling in AD mice causes abnormal processing of the amyloid precursor protein so that amyloid peptide production augments and neurotoxicity is induced. Taken together, the current evidences suggest that increased GSK-3 signalling may be responsible for the deficits in memory formation in early stages of AD and neurodegeneration in later stages of the disease. (C) 2009 IUBMB IUBMB Life, 61(5): 516-521, 2009
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