El factor de transcripción Nrf2 como nueva diana terapéutica para la Enfermedad de Parkinson

Résumé

Almost two hundred years past after it was fisrt described by the English doctor James Parkinson, Parkinson�s disease (PD) still remains to be mysterious and incurable. Our lack of real success in controlling the disease is in large part due to its enormous complexity. PD involves uncounted internal factors, such as genes (PARK genes) and their products the proteins, metabolites, electrophysiological features and external factors related to lifestyle choices and, presumably, exposures to pesticides (paraquat, rotenone) and other enviromental factors. But it is not enough by a long shot to list the many contributors to the disease. Instead, it is the system of functional interactions among these contributors that makes the disease so complicated. For instance, the factors listed above could affect the machinery of the antioxidant defense system and degradation, detoxication systems as autophagy, ubiqutin-proteasome or the Nrf2/Keap1 pathway, which are critically associated with PD. So the acumulative, synergistic and failure underlying of these biochemical processes, that span multiple levels in the biological hierarchy, promote neuronal loss over time. The purpose of this thesis is to study the neuroprotective role exerted by Nrf2/Keap1 antioxidant pathway and its intimate relationship with the autophagic process, demonstrating greater sensitivity in cells exposed to environmental agents that have an alteration in this pathway . The thesis is structured in six sections: 1) introduction to PD, 2) a list of the goals outlined in this paper, 3) description of the methodology followed, 4) presentation of the results obtained, 5) discussion of data within the scientific environment, 6) conclusions.