Identification of a risk transcriptome and proteome in Parkinson's disease, Dementia with Lewy bodies and rapidly progressive Dementia with Lewy bodies

Parkinson's disease (PD) is a neurodegenerative disorder characterized by movement impairment, or parkinsonism, for which there is still no cure. The manifest clinical signs result from neuronal loss of more than 60% in the substantia nigra pars compacta. Cognitive disorders and dementia in PD usually occur, thus leading to Parkinson disease with dementia (PDD). Moreover, Dementia with Lewy bodies (DLB) is also considered a neurodegenerative disease and one of the mostcommon causes of dementia, with cognitive impairment symptoms similar to Alzheimer-type dementia, and with parkinsonism. Its onset is insidious and is characterized by a slow progression in comparison with its fast form, also known as Dementia with Lewy bodies rapidly progressive (rpDCL), which appears suddenly and progresses quickly. In these pathologies there occurs a neural degeneration not only related to the accumulation of altered proteins, but more likely as a result of multiple deleterious factors. The hypothesis of this work is that the identification of molecular changes analyzed through the application of "-omics" techniques will be useful to obtain information about a risk transcriptome/proteome in the aforementioned diseases. Thus, the main objective of the present thesis is the identification of molecular alterations underlying functional cerebral changes and anatomical modifications in different brain regions and different Braak stages of PD, as well as DCL and DCLrp, with the use of post-mortem human brain samples compared with controls, combining microarray, mRNA, protein and enzyme assays studies. The obtained results have identified molecular alterations in PD, DLB, and rpDLB of different metabolic pathways including changes in the machinery of protein synthesis, in the mitochondrial energy metabolism, in neuroinflammation, in the purine pathway, and in new signaling pathways comprising olfactory and taste receptors paths.