Peripheral blood gene expression profiling of LRRK2 and Parkin monogenic forms of Parkinson’s disease for disease assessment

Parkinson's disease (PD) is a common, disabling, incurable and progressive neurodegenerative disease. It is mainly characterized by four primary symptoms: tremor, rigidity, bradykinesia and postural instability. Diagnosis is mainly clinically based on a physician's examination and on the response to therapy. Importantly, symtpoms appears after a very long pre-symptomatic phase when vulnerable dopamine neurons of the Substantia Nigra continuosly die. A general problem with neurological diseases is that the site of degeneration is not accessible for direct study during life. Although PD aetiology is still largely unknown, studies concerning genes mutated in familial PD (fPD), such as LRRK2 and Parkin, have greatly contributed to the current understanding of the disease. However, it is unclear whether different forms of genetic cases present common mechanisms of neurodegeneration as well as their relation with sporadic PD (sPD) that affects people in the majority. In this project, we interrogate the molecular processes perturbed in cellular blood of patients with LRRK2 and Parkin monogenic forms of Parkinson's disease for disease assessment. We are going to analyze blood from patients with G2019S mutation in LRRK2 gene, inactivating mutations in Parkin gene and healthy controls by mean of gene expression profiling. We will identify a set of genes whose expression is altered in PD. Our ultimate goal is to provide new cues about the relationship between different forms of fPD as well as their commonalities and differences with sPD. This may be important for the diagnosis of pre-symptomatic patients and for monitoring the effects of new therapeutic treatments.