Chlorinative stress: an under appreciated mediator of neurodegeneration?
Oxidative stress has been implicated as playing a role in neurodegenerative disorders, such as ischemic stroke, Alzheimer's, Huntington's, and Parkinson's disease. Persuasive evidences have shown that microglial-mediated oxidative stress contributes significantly to cell loss and accompanying cognitive decline characteristic of the diseases. Based on the facts that (i) levels of catalytically active myeloperoxidase are elevated in diseased brains and (ii) myeloperoxidase polymorphism is associated with the risk of developing neurodegenerative disorders, HOCl as a major oxidant produced by activated phagocytes in the presence of myeloperoxidase is therefore suggested to be involved in neurodegeneration. Its association with neurodegeneration is further showed by elevated level of 3-chlorotyrosine (bio-marker of HOCl in vivo) in affected brain regions as well as HOCl scavenging ability of neuroprotectants, desferrioxamine and uric acid. In this review, we will summary the current understanding concerning the association of HOCl and neuronal cell death where production of HOCl will lead to further formation of reactive nitrogen and oxygen species. In addition, HOCl also causes tissue destruction and cellular damage leading cell death.
Yap
Yann Wan
YW
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, Singapore 117597, Singapore.
Whiteman
Matthew
M
Cheung
Nam Sang
NS
D000544:Alzheimer Disease; D001921:Brain / Q000473:pathology*; D002545:Brain Ischemia; D006801:Humans; D006861:Hydrogen Peroxide; D006997:Hypochlorous Acid / Q000633:toxicity*; D008954:Models, Biological; D009103:Multiple Sclerosis; D009410:Nerve Degeneration / Q000209:etiology*; D019636:Neurodegenerative Diseases; D009474:Neurons / Q000473:pathology*; D018384:Oxidative Stress; D010300:Parkinson Disease; D010586:Phagocytes / Q000378:metabolism
D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide