miRNAs Profiling in Parkinson's Disease

Hypothesis and Significance:

The project intends to identify novel biomarkers for PD and clinical parameters related to the PD etiology. To do that circulating miRNA profiling through a next-generation sequencing will be performed using a single sample approach in the case-control study cohort and identified miRNAs will be validated by qRT-PCR and functional analyses. In addition, the project will contribute expanding the knowledge of the genetic architecture of PD taking advantage of genetic characterization of the study sample. miRNA genes and target genes will be used to prioritize genetic variants to be tested for association with PD to detect novel genes and functional variants that confer disease risk.

Specific Aim 1:

Profile of circulating miRNAs in the serum of PD patients and controls by next-generation sequencing in individual samples. Correlation between identified miRNAs and PD-related parameters and validation in independent cohorts

Specific Aim 2:

Bioinformatics prediction of target genes and miRNA functional validation

Specific Aim 3:

Identification of genes/genetic variants in miRNA pathways predisposing to PD

Expected outcomes:

The study will allow to discover novel circulating miRNAs as biomarkers for Parkinson's disease. As the deep phenotype characterization of the study sample, the project expects to find new associations of identified miRNAs with disease-related parameters and define the role of miRNAs in the physiological pathways in which those parameters are involved and in the etiology of PD. Also, the understanding of the genetics of the disease will open avenues for novel therapeutic strategies.

Inclusion criteria

for cases:

• Presence of at least two out the following cardinal signs: resting tremor, cogwheel rigidity, bradykinesia, asymmetrical onset of symptoms and symptomatic response to L-dopa (levodopa)

Exclusion criteria

for cases:

• Previous thalamotomy on the implanted sided, significant brain atrophy or structural damage seen on CT or MRI, marked cognitive dysfunction, active psychiatric symptoms, or concurrent neurological or other uncontrolled medical disorders.

Exclusion criteria

for controls:

Personal or family history for neurodegenerative diseases