Molecular Mechanism Linked to Juvenile Parkinson’s Identified

Scientists have discovered the molecular mechanism by which a mutation of the adenosine type 1 receptor gene is associated with juvenile Parkinson’s disease. Parkinson’s disease affects 3% of population over 65 years old, and the average age of onset is 60. The study was conducted by a group of researchers of the Faculty of Medicine and Health Sciences, the Institute of Neurosciences of the University of Barcelona (UBNeuro) and the Bellvitge Biomedical Research Institute (IDIBELL).

Young Onset Parkinson’s Disease: New Findings

The team, led by Professor Francisco Ciruela (UB-IDIBELL-UBNeuro), focused on the study of the mechanistic field of the mutation of the brain receptor, previously defined as the potential cause for the early disease. The results, presented in the journal Biomedicine and Pharmacotherapy, reveal that the mutation reduced this receptor’s ability to interact with other adenosine receptors —with the type 2receptor—, which would cause an increase in the neuronal circuits’ excitability in the brain region called the striatum.

“We propose that the inability of both adenosine receptors to interact would generate glutamatergic hyperexcitability in the neuronal circuits of the striatum, a key mechanism in the pathogenesis of juvenile Parkinson’s”, notes Francisco Ciruela, professor of the Department of Pathology and Experimental Therapeutics of the UB and head of the IDIBELL Research Group on Neuropharmacology and Pain.

An Imbalance in the Excitability of the Neuronal Circuit

Previously, their involvement in neurodegenerative pathologies such as Parkinson’s disease had already been suggested.

The studied mutation affects the type 1 adenosine receptor, which has an inhibitory effect on its counterpart —the type 2 adenosine receptor— through which it facilitates the glutamate release and the circuit’s excitability. According to the conclusions, the mutation would prevent the molecular and functional interaction of both adenosine receptors and, as a result, it would facilitate glutamate release, which would cause hyperexcitability in the striatum neuronal circuits.

The study includes the participation of research teams from the Autonomous University of Barcelona (UAB), the Luxembourg Institute of Health (LIH) and the National Institutes of Health (NIH) in Baltimore (United States).

Source-Eurekalert