Ontology highlight
ABSTRACT: Background
5-Lipoxygenase (5-LO) is a protein widely distributed in the central nervous system where it modulates amyloidosis and memory impairments in transgenic mouse models of Alzheimer's disease. However, no data are available as to whether 5-LO is elevated in human tauopathy or if it directly influences tau pathology in a relevant model of the disease.Methods
We assayed 5-LO levels in brain samples from patients with tauopathy and transgenic tau mice, and we evaluated the effect of 5-LO pharmacologic inhibition on the phenotype of these mice.Results
The 5-LO protein is upregulated in human tauopathy and transgenic tau mice brains. Pharmacologic blockade of 5-LO in tau mice resulted in significant memory improvement, rescue of synaptic integrity and dysfunction, and reduction of tau pathology via a cdk5-dependent mechanism.Conclusions
These results establish a key role of 5-LO in the development of the tau pathology phenotype and demonstrate it to be a novel viable therapeutic target for the pharmacologic treatment of human tauopathy.
SUBMITTER: Giannopoulos PF
PROVIDER: S-EPMC4529386 | biostudies-literature | 2015 Nov
REPOSITORIES: biostudies-literature
Giannopoulos Phillip F PF Chu Jin J Sperow Margaret M Li Jian-Guo JG Yu W Haung WH Kirby Lynn G LG Abood Mary M Praticò Domenico D
Biological psychiatry 20150207 10
<h4>Background</h4>5-Lipoxygenase (5-LO) is a protein widely distributed in the central nervous system where it modulates amyloidosis and memory impairments in transgenic mouse models of Alzheimer's disease. However, no data are available as to whether 5-LO is elevated in human tauopathy or if it directly influences tau pathology in a relevant model of the disease.<h4>Methods</h4>We assayed 5-LO levels in brain samples from patients with tauopathy and transgenic tau mice, and we evaluated the ef ...[more]