Abstract
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Brain Behav Immun. 2020 Aug;88:844-855. doi: 10.1016/j.bbi.2020.03.022. Epub 2020 Mar 25.
5-lipoxygenase pathway and its downstream cysteinyl leukotrienes as potential therapeutic targets for Alzheimer’s disease.
Chen F(1), Ghosh A(2), Lin J(2), Zhang C(3), Pan Y(4), Thakur A(5), Singh K(6), Hong H(7), Tang S(8).
Author information: (1)Department of Pharmacy, the First Affiliated Hospital of Xiamen University, Xiamen, China; Department of Pharmacology and Key Laboratory of Neuropsychiatric Diseases, China Pharmaceutical University, Nanjing, China. (2)Department of Pharmacology and Key Laboratory of Neuropsychiatric Diseases, China Pharmaceutical University, Nanjing, China. (3)School of Pharmacy, North China University of Science and Technology, Tangshan, China; Department of Pharmacology and Key Laboratory of Neuropsychiatric Diseases, China Pharmaceutical University, Nanjing, China. (4)Department of Medicine, Queen Mary Hospital, the University of Hong Kong, Hong Kong, China. (5)Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China. (6)Department of Biotechnology, Noida Institute of Engineering & Technology, Greater Noida, India. (7)Department of Pharmacology and Key Laboratory of Neuropsychiatric Diseases, China Pharmaceutical University, Nanjing, China. Electronic address: honghao@cpu.edu.cn. (8)Department of Pharmacology and Key Laboratory of Neuropsychiatric Diseases, China Pharmaceutical University, Nanjing, China. Electronic address: tang_susu@126.com.
5-lipoxygenase (ALOX5) is an enzyme involved in arachidonic acid (AA) metabolism, a metabolic pathway in which cysteinyl leukotrienes (CysLTs) are the resultant metabolites. Both ALOX5 and CysLTs are clinically significant in a number of inflammatory diseases, such as in asthma and allergic rhinitis, and drugs antagonizing the effect of these molecules have long been successfully used to counter these diseases. Interestingly, recent advances in ‘neuroinflammation’ research has led to the discovery of several novel inflammatory pathways regulating many cerebral pathologies, including the ALOX5 pathway. By means of pharmacological and genetic studies, both ALOX5 and CysLTs receptors have been shown to be involved in the pathogenesis of Alzheimer’s disease (AD) and other neurodegenerative/neurological diseases, such as in Parkinson’s disease, multiple sclerosis, and epilepsy. In both transgenic and sporadic models of AD, it has been shown that the levels of ALOX5/CysLTs are elevated, and that genetic/pharmacological interventions of these molecules can alleviate AD-related behavioral and pathological conditions. Clinical relevance of these molecules has also been found in AD brain samples. In this review, we aim to summarize such important findings on the role of ALOX5/CysLTs in AD pathophysiology, from both the cellular and the molecular aspects, and also discuss the potential of their blockers as possible therapeutic choices to curb AD-related conditions.
Copyright © 2020 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.bbi.2020.03.022 PMID: 32222525 [Indexed for MEDLINE]
Conflict of interest statement: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.