Oxygen neurodegenerative diseases

In many crucial biological processes, such as oxygen transport, electron transport, intermediary metabolism, metals play an important part. Therefore, disorders of metal homeostasis, metal bioavailability or toxicity caused by metal excess, are responsible for a large number of human diseases. We have already mentioned disorders of iron metabolism (see Chapter 7) and of copper metabolism (see Chapter 14). The important role, particularly of redox metals such as copper and iron, and also of zinc, in neurodegenerative diseases, such as Parkinson s disease, Alzheimer s disease, etc. has also been discussed (see Chapter 18). We will not further discuss them here. 

Neuronal cell death is required for the development of the nervous system. However, recent studies suggest that neurons die from programmed cell death (apoptosis) in brains deprived of oxygen by stroke [14] and trauma [15], and in the brains of Alzheimer s patients [16], Therefore, prevention of neuronal apoptosis has been considered to be a desirable therapeutic strategy for treating such neurodegenerative diseases, although the value of this approach is not yet evident. We have recently reported that crocin suppresses tumor necrosis factor (TNF)-a-... 

Floyd RA (1999) Neuroinflammatory processes are important in neurodegenerative diseases an hypothesis to explain the increased formation of reactive oxygen and nitrogen species as major factors involved in neurodegenerative disease development. Free Radic Biol Med 26 1346-1355... 

NADPH oxidases (NOX), catalyzing the reduction of molecular oxygen to form the superoxide radical anion (02 ) and hydrogen peroxide (H202), are involved in stroke, diabetes, atherosclerosis, and chronic neurodegenerative diseases. GKT136901 is a novel NOX-1/4 inhibitor with potential application in the areas of... 

Unbalanced production of reactive oxygen species, first of aU superoxide and hydrogen peroxide, has been postulated as playing a role in the pathogenesis of a number of chnical disorders, such as acute respiratory distress syndrome, ischemia-reperfusion injury, atherosclerosis, neurodegenerative diseases and cancer. As the function of SOD and CAT is the protection against oxidative stress, their apphcation has been proposed in cases where oxidative stress is important in the mechanism of a disease. 

Tabner BJ, Turnbull S, El-Agnaf O, Allsop D. Production of reactive oxygen species from aggregating proteins implicated in Alzheimer s disease, Parkinson s disease and other neurodegenerative diseases. Curr Top Med Chem 2001 1 507-17. 

Recall that oxidative stress results from reactive oxygen or nitrogen species that are not fully neutralized by anti-oxidants (see Chapter 24). The increase in reactive oxygen and nitrogen species results in protein, lipid, and nucleic acid modifications. Many neurodegenerative diseases, such as Alzheimer disease, Parkinson disease, and Lou Gehrig disease, have in common increased oxidative stress. 

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