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

• 5Lipoxygenase is upregulated in brain aging and Alzheimer’s disease.
• 5Lipoxygenase acts as an endogenous modulator of Aβ formation in vitro and in vivo.
• 5Lipoxygenase modulates the four components of the γ-secretase complex at the transcription levels without affecting Notch signaling.
• 5Lipoxygenase has a pleiotropic effect on the entire spectrum of the Alzheimer’s disease phenotype.
• 5Lipoxygenase is a viable therapeutic target for Alzheimer’s disease.

Alzheimer’s disease (AD) is an age-related, neurodegenerative disorder characterized by cognitive impairment with memory loss, extracellular amyloid beta (Aβ) 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 γ-secretase influences Aβ 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.