Iron and glutathione at the crossroad of redox metabolism in neurons.
Neurons, as non-dividing cells, encounter a myriad of stressful conditions throughout their lifespan. In particular, there is increasing evidence that iron progressively accumulates in the brain with age and that iron induced oxidative stress is the cause of several forms of neurodegeneration. Here, we review recent evidence that gives support to the following notions: 1) neuronal iron accumulation leads to oxidative stress and cell death; 2) neuronal survival to iron accumulation associates with decreased expression of the iron import transporter DMT1 and increased expression of the efflux transporter IREG1; and 3) the adaptive process of neurons towards iron-induced oxidative stress includes a marked increase in both the expression of the catalytic subunit of gamma glutamate-cysteine ligase and glutathione. These findings may help to understand aging-related neurodegeneration hallmarks: oxidative damage, functional impairment and cell death.
Aracena
Paula
P
Department of Biology, Faculty of Sciences and Cell Dynamic and Biotechnology Research Center, Universidad de Chile, Santiago, Chile.
Aguirre
Pabla
P
Muñoz
Pablo
P
Núñez
Marco T
MT
D000328:Adult; D000368:Aged; D027682:Cation Transport Proteins / Q000378:metabolism; D016923:Cell Death; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008875:Middle Aged; D009410:Nerve Degeneration / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2
D027682:Cation Transport Proteins; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; D007501:Iron; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2