期刊
CURRENT ALZHEIMER RESEARCH
卷 13, 期 6, 页码 621-630出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1567205013666160322142226
关键词
Alzheimer's disease; aggregation; animal models; cell models; intracellular A beta; oligomers; neurotoxicity; synaptic dysfunction
资金
- National Natural Science Foundation of China [31200583]
- Doctoral Program of Higher Education of China [20110091120045]
- State Key Laboratory of Molecular Biology
Accumulation of intraneuronal amyloid-beta peptide (A beta) appears to be an early event in Alzheimer's disease (AD), suggesting its important role in the neurodegenerative process of AD. It is indicated that intracellular A beta originates from a portion of A beta, which is not secreted and consequently remains intracellular, or alternatively from the secreted A beta, which is internalized into intracellular A beta pool. A number of cell and transgenic animal models are established to study the pathological role of intracellular A beta, and to screen for drugs against A beta aggregation and associated toxicity. A beta aggregates, particularly oligomers, may lead to synaptic dysfunction and neuronal loss. Screened from high-throughput methods, a number of cell-permeable agents reduce the aggregation of intracellular A beta and antagonize its cytotoxicity by inhibiting the formation of A beta oligomers in vivo. The multi-functional roles of A beta in alternate pathways and associated clinical implications for AD treatment are also discussed.
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