Peroxiredoxins in the central nervous system.
Oxidative stress is considered one of the causative pathomechanisms of nervous system diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, stroke and excitotoxicity. The basal expression of six different peroxiredoxin (Prx) isozymes show distinct distribution profiles in different brain regions and different cell types. PrxI and VI are expressed in glial cells but not in neurons; while PrxII, III, IV and V are expressed in neurons. Various diseases or models show altered expression levels of these isozymes, such as by upregulation of PrxI, II and VI and downregulation of PrxIII. Thioredoxin (Trx)I mRNA is distributed widely in the rat brain. This distribution pattern may reflect the specific functions of these isozymes. Recently, the neuroprotective roles of Prx III and V against ibotenate-induced-excitotoxicity were reported by two independent groups. Adenovirus transduction of PrxIII eliminated protein nitration and prevented gliosis caused by direct infusion of ibotenate. Systemic administration of recombinant PrxV diminished brain lesions in animals treated with ibotenate. In this chapter, we review the causative mechanisms of oxidative stress in neurodegenerative diseases, as well as describe the basal and disease-induced changes in Prxs/Trxs/Trx reductases expression levels and neuroprotective roles of Trxs and Prxs as demonstrated in overexpression models.
Hattori
Fumiyuki
F
Asubio Pharma Co. Ltd. Research park, Institute of Integrated Medical Research Keio University, School of Medicine, Tokyo, Japan.
Oikawa
Shinzo
S
D000256:Adenoviridae; D000818:Animals; D002493:Central Nervous System Diseases / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics / Q000628:therapy; D004195:Disease Models, Animal; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007051:Ibotenic Acid / Q000633:toxicity; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics / Q000628:therapy; D018696:Neuroprotective Agents / Q000378:metabolism* / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D014161:Transduction, Genetic
D018690:Excitatory Amino Acid Agonists; D007527:Isoenzymes; D018696:Neuroprotective Agents; D007051:Ibotenic Acid; D054464:Peroxiredoxins