Parkinson's disease: molecular risk factors.

Parkinson's disease (PD) is a progressive neurodegenerative disorder second only to Alzheimer's disease. Diagnosis remains clinical, based on phenotypic patterns. In the last decade many attempts to develop early differential pre-clinical markers have been reported. In this presentation, the molecular risk factors that may link between the etiopathogenesis leading to PD and peripheral markers will be discussed. Genetic variation known to be involved in familial forms of PD will be shown to be linked to sporadic cases, as for example leucine-rich repeat kinase 2 (LRRK2) that was found to regulate microRNA-mediated translation regulation. In addition postmortem microarray findings of transcription alterations will be compared to the peripheral findings of mRNA profiles. Molecular processes involved in ubiquitination and proteasome, autophagy, mitochondrial dysfunction and the nicotinic and adenosine A2 protection will be discussed. The question of what time-point should be used measuring the different markers and the course of the disease considered, and the future possibilities in exploring these techniques will be debated.