Molecular Interplay Among A Beta, Tau And 5-Lipoxygenase: Implications For Alzheimer?s Disease Therapy | 12516
Journal of Alzheimers Disease & Parkinsonism
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The 5-Lipoxygenase (5LO) is up regulated in Alzheimer?s disease (AD), and in vivo modulates the amyloidotic phenotype
of APP 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 pharmacologic approach by generating 3xTg mice deficient for 5LO,
and administering 3xTg mice which 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 A? 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.
Domenico Pratico is Professor of Pharmacology, Microbiology and Immunology and member of the Center for Translational Medicine at Temple
University Internationally known for his work on Alzheimer?s disease. He has authored over 195 articles, and has received many awards for his
research accomplishments including the Biomedicine Investigator Award for Excellence in Scientific Research, Irvine H. Page Award for Medical
Research, Neurosciences Education and Research Award, The Zenith Award from the Alzheimer?s Association, and the Dorothy Dillon Eweson
Lectureship. During his 18-year academic career he has trained over 16 postdoctoral fellows, mentored more than 15 graduate students with many
former trainees now heading up their own laboratories at other universities across the country
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