title: The 5-Lipoxygenase as modulator of Alzheimer's γ-secretase and therapeutic target.
abstract: 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.
authors.affiliation: Department of Pharmacology and Center for Translational Medicine, Temple University School of Medicine, Philadelphia, PA 19140, United States.
authors.forename: Jin
authors.initials: J
authors.lastname: Chu
authors.affiliation: Department of Pharmacology and Center for Translational Medicine, Temple University School of Medicine, Philadelphia, PA 19140, United States. Electronic address: praticod@temple.edu.
authors.forename: Domenico
authors.initials: D
authors.lastname: Praticò
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology* / Q000276:immunology / Q000628:therapy*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D006801:Humans
chemical_list: D001094:Arachidonate 5-Lipoxygenase; D053829:Amyloid Precursor Protein Secretases
keywords: 5-lipoxygenase; Alzheimer’s disease; Amyloid beta; γ-Secretase; γ-Secretase activating protein