Development of new diagnostic markers for Parkinson’s disease: mutations in TGFbeta/Smad

We have recently detected a new intracellular signaling pathway (TGF/ Smad3 ) that may be involved in Parkinson’s disease (PD). Smad3 null mice present early parkinsonism at 2 months of age, characterized by a strong striatal dopamine catabolism, selective dopaminergic neurodegeneration of substantia nigra pars compacta, decreased astrocytic and trophic support in the mesostriatal system, increased MAO- B in substantia nigra, and notably aggregation of α-synuclein in specific brain nuclei, including motor and cingulate cortex, substantia nigra, striatum and spinal cord, with post-traductional modifications similar to that detected on Lewy bodies from the human pathology. Furthermore, Smad3 deficient mice have cognitive deficits, which are characterized by inhibition in the formation of LTP and strong decrease in the adult hippocampal neurogenesis (Tapia-González et al., 2011; Tapia-González et al., 2013). In the current project, we are looking for mutations in the genes of the intracellular signaling pathway of TGFbeta/Smad in Parkinson patients with dementia and cognitive impairment. We have already developed the method of next sequencing generation, using Ion Torrent, for the detection of a panel of nine genes related to this intracellular pathway. In the current phase of the project, we are performing a retrospective study of association between genetic variants and phenotype in Parkinson’s patients, and we request DNA samples of Parkinson’s disease patients from the Spanish Banco Nacional de ADN.