Therapeutic approach to neurodegenerative diseases by medical gases: focusing on redox signaling and related antioxidant enzymes.
Oxidative stress in the central nervous system is strongly associated with neuronal cell death in the pathogenesis of several neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. In order to overcome the oxidative damage, there are some protective signaling pathways related to transcriptional upregulation of antioxidant enzymes, such as heme oxygenase-1 (HO-1) and superoxide dismutase (SOD)-1/-2. Their expression is regulated by several transcription factors and/or cofactors like nuclear factor-erythroid 2 (NF-E2) related factor 2 (Nrf2) and peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α). These antioxidant enzymes are associated with, and in some cases, prevent neuronal death in animal models of neurodegenerative diseases. They are activated by endogenous mediators and phytochemicals, and also by several gases such as carbon monoxide (CO), hydrogen sulphide (H(2)S), and hydrogen (H(2)). These might thereby protect the brain from severe oxidative damage and resultant neurodegenerative diseases. In this paper, we discuss how the expression levels of these antioxidant enzymes are regulated. We also introduce recent advances in the therapeutic uses of medical gases against neurodegenerative diseases.
Laboratory of Pathophysiology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Fukuoka 812-8582, Japan.
Kyota
K
Fujita
Megumi
M
Yamafuji
Yusaku
Y
Nakabeppu
Mami
M
Noda
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D005740:Gases / Q000627:therapeutic use*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000201:enzymology* / Q000378:metabolism; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
D000975:Antioxidants; D005740:Gases; D017382:Reactive Oxygen Species