期刊
MOLECULAR PSYCHIATRY
卷 19, 期 4, 页码 511-518出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/mp.2013.23
关键词
Alzheimer's disease; amyloid beta; 5-lipoxygenase; memory; synapse; tau protein; transgenic mouse models
资金
- US National Institute of Health (NIH) [AG033568, NS071096, P30 DA 13429, T32 DA 07237]
- Alzheimer Art Quilt Initiative
5-Lipoxygenase (5LO) is upregulated in Alzheimer's disease (AD) and in vivo modulates the amyloidotic phenotype of amyloid precursor protein transgenic mice. However, no data are available on the effects that 5LO has on synaptic function, integrity and cognition. To address this issue, we used a genetic and a pharmacological approach by generating 3 x Tg mice deficient for 5LO and administering 3 x Tg mice with a 5LO inhibitor. Compared with controls, we found that even before the development of overt neuropathology, both animals manifested significant memory improvement, rescue of their synaptic dysfunction and amelioration of synaptic integrity. In addition, later in life, these mice had a significant reduction of Ab and tau pathology. Our findings support a novel functional role for 5LO in regulating synaptic plasticity and memory. They establish this protein as a pleiotropic contributor to the development of the full spectrum of the AD phenotype, making it a valid therapeutic target for the treatment of AD.
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