Long-term treatment of thalidomide ameliorates amyloid-like pathology through inhibition of β-secretase in a mouse model of Alzheimer's disease.
Long-term treatment of thalidomide ameliorates amyloid-like pathology through inhibition of β-secretase in a mouse model of Alzheimer's disease.
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DOI：
10.1371/journal.pone.0055091
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Shen Y
中科院分区：
文献类型：
--
作者：
He P;Cheng X;Staufenbiel M;Li R;Shen Y
Thalidomide is a tumor necrosis factor alpha (TNFα) inhibitor which has been found to have abilities against tumor growth, angiogenesis and inflammation. Recently, it has been applied in clinic for the treatment of multiple myeloma as well as some inflammatory diseases. However, whether thalidomide has any therapeutic effects on neurodegenerative disorders, i.e. Alzheimer’s disease (AD) is not clear. AD is characterized by excessive amount of amyloid β peptides (Aβ), which results in a significant release of inflammatory factors, including TNFα in the brain. Studies have shown that inhibition of TNFα reduces amyloid-associated pathology, prevents neuron loss and improves cognition. Our recent report showed that genetic inhibition of TNFα/TNF receptor signal transduction down-regulates β amyloid cleavage enzyme 1 (BACE1) activity, reduces Aβ generation and improves learning and memory deficits. However, the mechanism of thalidomide involving in the mitigation of AD neuropathological features remains unclear. Here, we chronically administrated thalidomide on human APPswedish mutation transgenic (APP23) mice from 9 months old (an onset of Aβ deposits and early stage of AD-like changes) to 12 months old. We found that, in addition of dramatic decrease in the activation of both astrocytes and microglia, thalidomide significantly reduces Aβ load and plaque formation. Furthermore, we found a significant decrease in BACE1 level and activity with long-term thalidomide application. Interestingly, these findings cannot be observed in the brains of 12-month-old APP23 mice with short-term treatment of thalidomide (3 days). These results suggest that chronic thalidomide administration is an alternative approach for AD prevention and therapeutics.
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影响因子：
6
作者：
Janelsins, Michelle C.;Mastrangelo, Michael A.;Bowers, William J.
通讯作者：
Bowers, William J.
DOI：
10.1016/s0006-291x(03)01270-1
发表时间：
2003-08-08
影响因子：
3.1
作者：
Hong, HS;Hwang, EM;Mook-Jung, I
通讯作者：
Mook-Jung, I
小胶质细胞激活与增强的肿瘤坏死因子-Alpha和单核细胞化学吸收剂蛋白-1表达的早期相关性在三重转基因阿尔茨海默氏病小鼠的内嗅皮层中特异性。
影响因子：
9.3
作者：
Janelsins, Michelle C.;Mastrangelo, Michael A.;Oddo, Salvatore;LaFerla, Frank M.;Federoff, Howard J.;Bowers, William J.
通讯作者：
Bowers, William J.
DOI：
10.1083/jcb.200705042
发表时间：
2007-08-27
期刊：
The Journal of cell biology
影响因子：
--
作者：
He P;Zhong Z;Lindholm K;Berning L;Lee W;Lemere C;Staufenbiel M;Li R;Shen Y
通讯作者：
Shen Y
影响因子：
3.5
作者：
Hussain, I;Powell, D;Christie, G
通讯作者：
Christie, G