Effect of overexpression of wild-type and mutant Cu/Zn-superoxide dismutases on oxidative damage and antioxidant defences: relevance to Down's syndrome and familial amyotrophic lateral sclerosis

2001 ◽  
Vol 76 (4) ◽  
pp. 957-965 ◽  
Author(s):  
MoonHee Lee ◽  
Dong-Hoon Hyun ◽  
Peter Jenner ◽  
Barry Halliwell
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Oxidative Damage ◽  
Down's Syndrome ◽  
Down’S Syndrome ◽  
Superoxide Dismutases ◽  
Familial Amyotrophic Lateral Sclerosis ◽  
Wild Type ◽  
Antioxidant Defences ◽  
Lateral Sclerosis

Free Radicals in Down's Syndrome, Amyotrophic lateral sclerosis & Rheumatoid Arthritis

2017 ◽  
Author(s):  
Luke Sammut
Keyword(s):  
Rheumatoid Arthritis ◽  
Amyotrophic Lateral Sclerosis ◽  
Free Radicals ◽  
Free Radical ◽  
Transition Metals ◽  
Tissue Injury ◽  
Down's Syndrome ◽  
Down’S Syndrome ◽  
Antioxidant Defences ◽  
Lateral Sclerosis

A free radical is an atom or group of atoms that have one or more unpaired electrons that can be considered as fragments of molecules and which are generally very reactive. Free Radicals can have positive, negative or neutral charge. They are produced continuously in cells either as accidental by-products of metabolism or deliberately during, for example, phagocytosis. The most important reactants in free radical biochemistry in aerobic cells are oxygen and its radical derivatives (superoxide and hydroxyl radical), hydrogen peroxide and transition metals. Cells have developed a comprehensive array of antioxidant defences to prevent free radical formation or limit their damaging effects. These include enzymes to decompose peroxides, proteins to sequester transition metals and a range of compounds to ‘scavenge’ free radicals. Reactive free radicals formed within cells can oxidise biomolecules and lead to cell death and tissue injury. Establishing the involvement of free radicals in the pathogenesis of a disease is extremely difficult due to the short lifetimes of these species. We describe the role of free radicals in Down's syndrome, Amyotrophic lateral sclerosis and Rheumatoid arthritis.

Free Radicals in Down's Syndrome, Amyotrophic lateral sclerosis & Rheumatoid Arthritis

2017 ◽  
Author(s):  
Luke Sammut
Keyword(s):  
Rheumatoid Arthritis ◽  
Amyotrophic Lateral Sclerosis ◽  
Free Radicals ◽  
Free Radical ◽  
Transition Metals ◽  
Tissue Injury ◽  
Down's Syndrome ◽  
Down’S Syndrome ◽  
Antioxidant Defences ◽  
Lateral Sclerosis

A free radical is an atom or group of atoms that have one or more unpaired electrons that can be considered as fragments of molecules and which are generally very reactive. Free Radicals can have positive, negative or neutral charge. They are produced continuously in cells either as accidental by-products of metabolism or deliberately during, for example, phagocytosis. The most important reactants in free radical biochemistry in aerobic cells are oxygen and its radical derivatives (superoxide and hydroxyl radical), hydrogen peroxide and transition metals. Cells have developed a comprehensive array of antioxidant defences to prevent free radical formation or limit their damaging effects. These include enzymes to decompose peroxides, proteins to sequester transition metals and a range of compounds to ‘scavenge’ free radicals. Reactive free radicals formed within cells can oxidise biomolecules and lead to cell death and tissue injury. Establishing the involvement of free radicals in the pathogenesis of a disease is extremely difficult due to the short lifetimes of these species. We describe the role of free radicals in Down's syndrome, Amyotrophic lateral sclerosis and Rheumatoid arthritis.

scholarly journals Fully Metallated S134N Cu,Zn-Superoxide Dismutase Displays Abnormal Mobility and Intermolecular Contacts in Solution

2005 ◽  
Vol 280 (43) ◽  
pp. 35815-35821 ◽  
Author(s):  
Lucia Banci ◽  
Ivano Bertini ◽  
Nicola D'Amelio ◽  
Elena Gaggelli ◽  
Elisa Libralesso ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Superoxide Dismutase ◽  
Familial Amyotrophic Lateral Sclerosis ◽  
Wild Type ◽  
Mutant Sod1 ◽  
Copper Zinc Superoxide Dismutase ◽  
Intermolecular Contacts ◽  
Nmr Methods ◽  
The Individual ◽  
Lateral Sclerosis

S134N copper-zinc superoxide dismutase (SOD1) is one of the many mutant SOD1 proteins known to cause familial amyotrophic lateral sclerosis. Earlier studies demonstrated that partially metal-deficient S134N SOD1 crystallized in filament-like arrays with abnormal contacts between the individual protein molecules. Because protein aggregation is implicated in SOD1-linked familial amyotrophic lateral sclerosis, abnormal intermolecular interactions between mutant SOD1 proteins could be relevant to the mechanism of pathogenesis in the disease. We have therefore applied NMR methods to ascertain whether abnormal contacts also form between S134N SOD1 molecules in solution and whether Cys-6 or Cys-111 plays any role in the aggregation. Our studies demonstrate that the behavior of fully metallated S134N SOD1 is dramatically different from that of fully metallated wild type SOD1 with a region of subnanosecond mobility located close to the site of the mutation. Such a high degree of mobility is usually seen only in the apo form of wild type SOD1, because binding of zinc to the zinc site normally immobilizes that region. In addition, concentration-dependent chemical shift differences were observed for S134N SOD1 that were not observed for wild type SOD1, indicative of abnormal intermolecular contacts in solution. We have here also established that the two free cysteines (6 and 111) do not play a role in this behavior.

scholarly journals Evidence of Increased Oxidative Damage in Both Sporadic and Familial Amyotrophic Lateral Sclerosis

2002 ◽  
Vol 69 (5) ◽  
pp. 2064-2074 ◽  
Author(s):  
Robert J. Ferrante ◽  
Susan E. Browne ◽  
Leslie A. Shinobu ◽  
Allen C. Bowling ◽  
M. Jay Baik ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Oxidative Damage ◽  
Familial Amyotrophic Lateral Sclerosis ◽  
Lateral Sclerosis
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