Role of the Glyoxalase System in Alzheimer’s Disease

Article type: Review Article

Authors: Jiang, Lianying^{a; 1} | Wang, Jiafeng^{a; 1} | Wang, Zhigang^b | Huang, Wenhui^c | Yang, Yixia^a | Cai, Zhiyou^{d; *} | Li, Keshen^{e; *}

Affiliations: [a] Department of Neurology, Stem Cell Research and Clinical Translation Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China | [b] Department of Neurosurgery, Jiangxi Medical College of Nanchang University, Nanchang, Jiangxi, China | [c] Department of Neurology and Stroke Center, the First Affiliated Hospital, Jinan University, Guangzhou, China | [d] Department of Neurology, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing, People’s Republic of China | [e] Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China; Clinical Neuroscience Institute of Jinan University, Guangzhou, China

Correspondence: [*] Correspondence to: Keshen Li, PhD, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, China; Clinical Neuroscience Institute of Jinan University, Guangzhou, China. Tel.: +86 18664641020; E-mail: likeshen1971@126.com and Zhiyou Cai, Department of Neurology, Chongqing General Hospital, University of Chinese Academy of Sciences, NO. 312 Zhongshan First Road, Yuzhong District, Chongqing, 400013 People’s Republic of China, Chongqing 400013, Tel./Fax: +86 23 63515796; E-mail: c0909@hotmail.com.

Note: [1] These authors contributed equally to this work.

Abstract: Alzheimer’s disease (AD) is an insidious and progressive neurodegenerative disease. The main pathological features of AD are the formation of amyloid-β deposits in the anterior cerebral cortex and hippocampus as well as the formation of intracellular neurofibrillary tangles. Thus far, accumulating evidence shows that glycation is closely related to AD. As a final product resulting from the crosslinking of a reducing sugar or other reactive carbonyls and a protein, the advanced glycation end products have been found to be associated with the formation of amyloid-β and neurofibrillary tangles in AD. As a saccharification inhibitor, the glyoxalase system and its substrate methylglyoxal (MG) were certified to be associated with AD onset and development. As an active substance of AGEs, MG could cause direct or indirect damage to nerve cells and tissues. MG is converted to D-lactic acid after decomposition by the glyoxalase system. Under normal circumstances, MG metabolism is in a dynamic equilibrium, whereas MG accumulates in cells in the case of aging or pathological states. Studies have shown that increasing glyoxalase activity and reducing the MG level can inhibit the generation of oxidative stress and AGEs, thereby alleviating the symptoms and signs of AD to some extent. This paper focuses on the relevant mechanisms of action of the glyoxalase system and MG in the pathogenesis of AD, as well as the potential of inhibiting the production of advanced glycation end products in the treatment of AD.

Keywords: Advanced glycation end product, Alzheimer’s disease, glutathione, glyoxalase system, methylglyoxal

DOI: 10.3233/JAD-180413

Journal: Journal of Alzheimer's Disease, vol. 66, no. 3, pp. 887-899, 2018