The 5-Lipoxygenase as modulator of Alzheimer's γ-secretase and therapeutic target

Alzheimer's disease (AD) is an age-related, neurodegenerative disorder characterized by cognitive impairment with memory loss, extracellular amyloid beta (A beta) peptides aggregation, and intracellular hyper-phosphorylated tau neurofibrillary tangles (NFT) accumulation. Although the 5-lipoxygenase (5LO) protein enzyme is well known as an important modulators of oxidation and inflammation, recent work has highlighted the new hypothesis that this pathway may play a direct role in AD pathogenesis. In this review article, we will discuss how the 5LO via the gamma-secretase influences A beta peptides formation, and other molecular pathologies including neuroinflammation, synaptic integrity, and cognitive functions, and provide an assessment of how targeting this protein could lead to novel therapeutics for AD and other related neurodegenerative disorders. (C) 2016 Elsevier Inc. All rights reserved.