Neurodegenerative diseases
The works that relate the importance of oxidative / nitrooxidative stress in the onset and progression of neurodegenerative diseases such as Alzheimer's (AD), Parkinson's (PD), amyotrophic lateral sclerosis (ALS), Huntington (HD) among others (Halliwell) are very extensive. 2006; Chisten, 2000).
The central nervous system, due to its biochemical and cytological characteristics, makes it a tissue vulnerable to the action of numerous cytotoxic agents. The brain is the organ most susceptible to oxidative damage due to high oxygen consumption, low levels of antioxidant enzymes (catalase and glutathione peroxidase), high concentrations of iron, which acts as a catalyst for the formation of the hydroxyl radical, and its capacity as oxidizing The excessive increase of reactive species produces a chronic inflammatory response, excitotoxicity due to the metabolites generated, and mitochondrial dysfunction (L?pez et al. 2014).
Neurons are particularly vulnerable to attack by RL and lipid peroxidation due to their high concentration of AGPI n-3 and AGPI n-6 and produce, as noted, a series of secondary products responsible for large cell damage. Peroxidation of membrane lipids affects neuronal homeostasis that produces an increase in membrane stiffness, decreased activity of membrane-bound enzymes, destruction of membrane receptors, and change in permeability (Wong- Ekkabut et al 2007; Olanow, 1993)
It has been observed that dopaminergic neurons are especially sensitive to oxidative stress, due to their high metabolic rate of O2 and also to the oxidation of dopamine (DA), either by autooxidation or by the metabolic pathway of the mono amine oxidase MAO. Many of the processes involved in oxidative stress and oxidative damage in PD, are the actions of monoamine oxidase B (MAO-B), essential for the enzymatic conversion of dopamine to hydrogen peroxide (L?pez. 2008
El papel del da?o oxidativo inducido por radicales libres en la patog?nesis de enfermedades neurodegenerativas ha sido definitivamente establecida (Galbusera et al. 2004). Entre las evidencias de la implicaci?n de la peroxidaci?n lip?dica en las enfermedades neurodegenertivas tenemos estudios post mortem y experimentales donde se observ? que existe un aumento de los marcadores de peroxidaci?n lip?dica, incluidas las sustancias reactivas al ?cido tiobarbit?rico (TBARS), malonil-dialdeh?do (MDA), 4-hidroxi-2-nonenal (HNE) y algunos isoprostanos en muestras postmortem de substancia nigra procedentes de cerebros de individuos con EP (Butterfield et al. 2010) y con EA. (Jeanner, 1995; Lovell. 1995; Jim?nez.2006).
Se han encontrado altas concentraciones de F2-IsoPs, los indicadores m?s precisos de estr?s y espec?fico para la peroxidaci?n lip?dica, en los tejidos del cerebro y fluidos corporales en numerosas enfermedades neurodegenerativas, incluyendo la Enfermedad de Alzheimer (Sultana et al. 2010), la Enfermedad de Parkinson (Farooqui et al.2011), la Enfermedad de Huntington (HD) (Sultana et al. 2013); (Montine et al. 1999), y la esclerosis lateral amiotr?fica (ALS) (Mitsumoto et al.2008) Recientemente se ha descrito un incremento de los isoprostanos, biomarcador de peroxidaci?n del AA por RL, en el L?quido C?falo Raqu?deo (LCR), en el plasma y la orina de pacientes con un deterioro cognitivo leve; se piensa que estas alteraciones est?n presentes antes del comienzo sintom?tico de la demencia (Practico et al, 2002).
The increase in ERO is partly due to antioxidant enzymes, catalase, glutathione peroxidase, showing reduced activity in brains of individuals with PD and AD. In addition, it has been observed in individuals with PD that reduced glutathione (GSH), the most important intracellular molecule in terms of the elimination of hydroperoxides in the brain, is decreased in the nigra substance, which causes the inactivation of peroxide of hydrogen and increase the formation of hydroxyl radicals (Dorado et al, 2004). It is considered that the decrease in GSH levels may be an early indicator of the PD process, as this also occurs in Parkinson's presymptomatic disease. GSH is lost only from the substance nigra in Parkinson's disease and this decrease is not observed in other areas of the brain or in other neurodegenerative diseases that affect this region. (Owen et al. 1996). Another neurodegenerative pathology associated with OE is amyotrophic lateral sclerosis, in which it has been observed that individuals with this pathology present mutations in the CuZnSOD gene, a mutation that causes the accumulation of ROS, oxidative stress and lipid peroxidation (Peterson. 2007) .
The study of EO and lipid peroxidation in cardiovascular diseases, cancer, diabetes, and neurodegenerative among others, has provided very important data on its pathogenic mechanism. In addition, biomarkers of lipid peroxidation such as isoprostans and neuroprostans, despite their cost and complexity, currently represent a very useful tool for the diagnosis and monitoring of the progress or efficacy of therapies in patients with pathologies possibly associated with OE and lipid peroxidation.
