5-Lipoxygenase as an emerging target against age-related brain disorders

Mengdie Yan; Siran Zhang; Chengtan Li; Yanyan Liu; Jianbo Zhao; Yanfang Wang; Yi Yang; Lihui Zhang

doi:10.1016/j.arr.2021.101359

5-Lipoxygenase as an emerging target against age-related brain disorders

Ageing Res Rev. 2021 Aug:69:101359. doi: 10.1016/j.arr.2021.101359. Epub 2021 May 10.

Authors

Mengdie Yan¹, Siran Zhang², Chengtan Li¹, Yanyan Liu¹, Jianbo Zhao³, Yanfang Wang³, Yi Yang⁴, Lihui Zhang⁵

Affiliations

¹ College of Pharmacy, School of Medicine, Hangzhou Normal University, Hangzhou, 311121, China; Hangzhou Key Laboratory of Medical Neurobiology, Hangzhou Normal University, Hangzhou, 311121, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, China.
² Department of Neurology, Zhejiang Hospital, Hangzhou, 310030, China.
³ College of Pharmacy, School of Medicine, Hangzhou Normal University, Hangzhou, 311121, China; Hangzhou Key Laboratory of Medical Neurobiology, Hangzhou Normal University, Hangzhou, 311121, China.
⁴ College of Pharmacy, School of Medicine, Hangzhou Normal University, Hangzhou, 311121, China; Hangzhou Key Laboratory of Medical Neurobiology, Hangzhou Normal University, Hangzhou, 311121, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, China. Electronic address: yyang@hznu.edu.cn.
⁵ College of Pharmacy, School of Medicine, Hangzhou Normal University, Hangzhou, 311121, China; Hangzhou Key Laboratory of Medical Neurobiology, Hangzhou Normal University, Hangzhou, 311121, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, China. Electronic address: lhzhang@hznu.edu.cn.

PMID: 33984528
DOI: 10.1016/j.arr.2021.101359

Abstract

Neuroinflammation is a common feature of age-related brain disorders including Alzheimer's disease (AD), Parkinson's disease (PD) and cerebral ischemia. 5-lipoxygenase (5-LOX), a proinflammatory enzyme, modulates inflammation by generating leukotrienes. Abnormal activation of 5-LOX and excessive production of leukotrienes have been detected in the development of age-related brain pathology. In this review, we provide an update on the current understanding of 5-LOX activation and several groups of functionally related inhibitors. In addition, the modulatory roles of 5-LOX in the pathogenesis and progression of the age-related brain disorders have been comprehensively highlighted and discussed. Inhibition of 5-LOX activation may represent a promising therapeutic strategy for AD, PD and cerebral ischemia.

Keywords: 5-lipoxygenase; Ageing; Brain; Inhibitor; Leukotriene; Neuroinflammation.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Alzheimer Disease*
Arachidonate 5-Lipoxygenase
Brain Ischemia*
Humans
Inflammation
Leukotrienes

Substances

Leukotrienes
Arachidonate 5-Lipoxygenase