title: The 12/15-lipoxygenase as an emerging therapeutic target for Alzheimer's disease.
abstract: Alzheimer's disease (AD) is a chronic neurodegenerative condition characterized by progressive memory loss. Mutations in genes involved in the production of amyloid-β (Aβ) are linked to the early-onset variant of AD. However, the most common form, sporadic AD, is considered to be the result of an interaction between environmental risk factors and various genes. Among them, recent work has highlighted the potential role that the 12/15-lipoxygenase (12/15LO) pathway may play in AD pathogenesis. 12/15LO is widely distributed in the central nervous system, and its levels are upregulated in patients with AD or mild cognitive impairments. Studies using animal models have implicated 12/15LO in the molecular pathology of AD, including the metabolism of Aβ and tau, synaptic integrity, and cognitive functions. We provide an overview of this pathway and its relevance to AD pathogenesis, discuss the mechanism(s) involved, and provide an assessment of how targeting 12/15LO could lead to novel AD therapeutics.
authors.affiliation: Department of Pharmacology and Center for Translational Medicine, Temple University School of Medicine, Philadelphia, PA 19140.
authors.forename: Yash B
authors.initials: YB
authors.lastname: Joshi
authors.affiliation: Department of Pharmacology and Center for Translational Medicine, Temple University School of Medicine, Philadelphia, PA 19140.
authors.forename: Phillip F
authors.initials: PF
authors.lastname: Giannopoulos
authors.affiliation: Department of Pharmacology and Center for Translational Medicine, Temple University School of Medicine, Philadelphia, PA 19140.
authors.forename: Domenico
authors.initials: D
authors.lastname: Praticò
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism* / Q000502:physiology; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D008568:Memory; D009435:Synaptic Transmission; D016875:tau Proteins / Q000378:metabolism
chemical_list: C475064:12-15-lipoxygenase; D016229:Amyloid beta-Peptides; D016875:tau Proteins; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase
keywords: 12/15-lipoxygenase; Alzheimer's disease; amyloid β; behavior; synapse; tau protein; therapeutics; transgenic mouse models