ANALYSIS OF FUNCTIONAL AND POST-TRASLATIONAL MODIFICATIONS IN ABNORMAL RED CELLS FROM NEUROACANTHOCYTOSIS

Neuroacanthocytosis syndromes group the autosomal recessive chorea-acanthocytosis and the X-linked McLeod Syndrome. The common neurological manifestations are dyskinesias, cognitive deterioration and progressive neurodegeration associated with the presence in peripheral circulation of red cell characterized by thorn or spur-like protrusion, known as acanthocytosis. Although different molecular defects have been identified associated with chorea-acanthocytosis phenotype (VPS13A, XK, JPH3 and PANK2 genes), the pathophysiology of these disorders and of the related abnormalities in red cells are still under investigation. The enormous gap between genotype and phenotype in NA patients suggests that post-translational modifications, such as phosphorylation, might be important in clinical manifestations of NA. The recent development of proteomic technologies allows fine proteins identification and proteins characterization in cell models. In the proposed project, we propose a multidisciplinary approach to study red cell abnormalities in neuro-acanthocytosis. The project has the following aims: 1; Characterization of red cell parameters and red cell membrane ion pathways, which may play an important role in generating acanthocytic red cells. 2; Characterization of red cell membrane phosphoproteome and identification of the differently proteins in ChCA and MLS compared to normal controls. The present project will offer the possibility to progress in the disease knowledge and to possibly identify new disease markers useful for diagnosis and/or clinical patients’ follow-up.