Amyotrophic lateral sclerosis antioxidants

Longnecker, M.P., Kamel, F., Umbach, D.M., Munsal, T.L., Shefuer, J.M., Lansdell, L.W., and Sandler, D.P. 2000. Dietary intake of calcium, magnesium and antioxidants in relation to risk of amyotrophic lateral sclerosis. Neuroepidemiology 19, 210-216. 

Orrell RW, Lane RJM, Ross M (2005) Antioxidant treatment for amyotrophic lateral sclerosis/motor neuron disease. The Cochrane Database for Systematic Reviews, Volume 4, The Cochrane Collaboration. 

Amyotrophic lateral sclerosis is currently treated with riluzole, which improves survival in 30% of patients. Riluzole, an NMDA receptor antagonist, is discussed later in this chapter. A clinical trial of gabapentin, a (y aminobutyric acid (GABA) agonist, in amyotrophic lateral sclerosis demonstrated little efficacy. Antioxidants have also not demonstrated significant efficacy so far. 

Antioxidant enzymes do not always protect us. There was great excitement when it was found that victims of a hereditary form of the terrible neurological disease amyotrophic lateral sclerosis (ALS see also Chapter 30) carry a defective gene for Cu / Zn-superoxide dismutase (SOD Eq. 16-27). This discovery seemed to support the idea that superoxide anions in the brain were killing neurons. However, it now appears that in some cases of ALS the defective SOD is too active, producing an excess of H2O2, which damages neurons. 

Acronyms and abbreviations PHSl, Physician s Health Study I CHAOS, Cambridge Heart Antioxidant Study ATBC, Alpha-Tocopherol, Beta-Carotene Cancer Prevention Stirdy NHS, Nurses Healtli Study CVD, cardiovascular disease ALS, amyotrophic lateral sclerosis NMD A, A-methyl-D-aspartate glutamate receptors. 

Petri S, Kiaei M, Damiano M, Hiller A, WiUe E, Manfredi G, CaUngasan NY, Szeto HH, Beal MF (2006) CeU-permeable peptide antioxidants as a novel therapeutic approach in a mouse model of amyotrophic lateral sclerosis. J Neurochem 98 1141-1148 Planells-Cases R, Lerma J, Ferrer-Montiel A (2006) Pharmacological intervention at ionotropic glutamate receptor complexes. Curr Pharm Des 12 3583-3596 Postina R (2008) A closer look at alpha-secretase. Curr Alzheimer Res 5 179-186 Price JL, Morris JC (1999) Tangles and plaques in nondemented aging and preclinical Alzheimer s disease. Ann Neurol 45 358-368... 

Placebo-controlled studies Valproic add is a histone deacetylase inhibitor which has antioxidative and antiapoptotic properties and reduced glutamate toxicity in preclini-cal studies. It has therefore been evaluated in a double-blind, placebo-controUed study in 163 patients with amyotrophic lateral sclerosis, who were randomized to valproate 1500 mg/day or placebo [342. Valproate did not affect survival or the rate of decline of functional status. The most frequent adverse events were diarrhea ( = 16 versus 14 with placebo), nausea (15 versus 12), vomiting (0 versus 3), abdominal pain (14 versus 15), increased appetite (19 versus 17), reduced appetite (17 versus 20), weight gain (20 versus 19), and tremor (39 versus 40). One patient taking valproate withdrew because of severe cognitive impairment. 

The SDEL algorithm has also been used to study the folding of more complicated systems, such as the wild-type human Cu, Zn superoxide dismu-tase (SOD) dimer. SOD is a 153-residue, homodimeric, antioxidant enzyme that dismutates superoxide ion to hydrogen peroxide and oxygen.It is an eight-strand, flattened, fl-barrel protein with one copper and one zinc ion per monomer.This protein is involved in the familial form of amyotrophic lateral sclerosis (FALS). 

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