ROLE OF PROTEIN OXIDATIVE MODIFICATIONS IN GENETIC NEURODEGENERATIVE DISEASES

An innovative approach to investigate the molecular basis of the genetically-linked neurodegenerative diseases, amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD), is proposed. In ALS and HD, as well as in other neurodegenerative diseases, what is called "oxidative stress" has a central role in the pathogenesis. Oxidative stress is an increased production of free radicals in cells or an increased susceptibility of the cells to free radicals, which are normally produced during cellular metabolism. All the studies on oxidative damage are limited by the fact that the molecular targets undergoing oxidation are very often not known. This project aims at identifying proteins undergoing abnormal oxidative modifications. This will be done using innovative technologies grouped under the term "proteomics". With this approach not the genes but the product genes, the proteins, eventually oxidatively modified, will be identified. The set up of the methods will be performed using neuronal cell cultures. Subsequently, the methods will be applied to analyze the cellular and animal models of ALS and HD. The identifications of specific proteins oxidatively modified may be the basis for the development of therapies (pharmacological and not) to cure and/or prevent ALS and MH, but also other neurodegenerative diseases with similar pathogenic mechanism.