Zileuton

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- Zileuton -

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Observations:

Zileuton

See also,

Zileuton, an FDA approved inhibitor of 5-lipoxygenase typically used to treat asthma

Pharmacologic Blockade of 5-Lipoxygenase Improves the Amyloidotic Phenotype of an Alzheimer's Disease Transgenic Mouse Model: Involvement of γ-Secretase.
Jin Chua and Domenico Pratic.
The American Journal of Pathology, Volume 178, Issue 4, April 2011, Pages 1762-1769
Abstract

The 5-lipoxygenase (5-LO) enzyme is widely distributed within the central nervous system. Previous works showed that this protein is up-regulated in Alzheimer's disease (AD) and that its genetic absence results in a reduction of amyloid β (Aβ) levels in Tg2576 mice. In the present study, we examined the effect of 5-LO pharmacological inhibition on the amyloidotic phenotype of these mice. Aβ deposition in the brains of mice receiving zileuton, a selective and specific 5-LO inhibitor, was significantly reduced when compared with control Tg2576 mice receiving vehicle. This reduction was associated with a similar decrease in brain Aβ peptides levels. Zileuton treatment did not induce any change in the steady state levels of amyloid-β precursor protein (APP), BACE1 or ADAM10. By contrast, it resulted in a significant reduction of presenilin 1 (PSEN1, alias PS1), nicastrin (NCSTN) , presenilin enhancer 2 homolog (PSNEN, alias, Pen-2), and anterior pharynx defective 1 (APH-1), the four components of the γ-secretase complex-at the protein and message level. Furthermore, in vitro studies confirmed that zileuton prevents Aβ formation by modulating γ-secretase complex levels without affecting Notch signaling. These data establish a functional role for 5-LO in the pathogenesis of AD-like amyloidosis, whereby it modulates the γ-secretase pathway. They suggest that pharmacological inhibition of 5-LO could provide a novel therapeutic opportunity for AD.
PMID:21435457
http://www.ncbi.nlm.nih.gov/pubmed/21435457

5-lipoxygenase protein modulates amyloid beta formation linked to Alzheimer's disease
Published on November 18, 2010 at 1:36 AM
http://www.news-medical.net/news/20101118/5-lipoxygenase-protein-modulates-amyloid-beta-formation-linked-to-Alzheimers-disease.aspx

Asthma drug shows promise in treatment of Alzheimer's disease
by Yasser Ali - March 27, 2011
http://www.themedguru.com/20110327/newsfeature/asthma-drug-shows-promise-treatment-alzheimers-disease-86144166.html

Scientists Discover Possible Treatment For Alzheimer's Disease In Asthma Drug
by T Goodman
http://inventorspot.com/articles/scientists_discover_possible_treatment_alzheimers_disease_asthma

Asthma drug could help fight Alzheimer's disease
2011-03-26 12:00:00
http://www.sify.com/news/asthma-drug-could-help-fight-alzheimer-s-disease-news-international-ld0mahhhcea.html

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