Classical proteomic techniques have been used in medicine for biomarker discovery and have recently entered the arena of neurodegenerative disorders. Biomarkers for disorders such as Huntington’s, Parkinson’s and Alzheimer’s diseases are currently being developed and tested for use in early detection, disease progression, prognosis and response to treatment. However, psychiatric disorders have been less researched to date. In this thesis, a classic proteomic approach was used (1) to examine alterations in molecular pathways determined by a well known high-risk schizophrenia (SCZ) gene (DISCI); (2) to assert the effects of antipsychotic medication in the brain and plasma of F344 rats; and (3) to canvass the plasma of psychotic patients searching for biomarkers of the disease. It was found that DISCI modulated the expression of dihydropteridine reductase, a key enzyme for biogenic amine synthesis and that of peptidyl-prolyl isomerase A, a protein involved in apoptosis. Antipsychotic treatment in rats exerted an effect on glucose and lipid metabolic pathways, mitochondria! function, immune system response, neuronal migration, differentiation and apoptosis. Alterations in calcium signalling pathways were detected in the plasma of psychotic patients, indicated by a significant reduction in plasma levels ofgelsolin and an increment of S100B.
Applied Proteomics: Using the Peripheral Proteome to Identify a Surrogate Marker of Schizophrenia
Sainz-Fuertes, R. (Author). 2012
Student thesis: Doctoral Thesis › Doctor of Philosophy