Purinergic Signalling in Parkinson’s Disease: A Multi-target System to Combat Neurodegeneration

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, characterized by progressive loss of dopaminergic neurons that results in characteristic motor and non-motor symptoms. l-3,4 dihydroxyphenylalanine (l-DOPA) is the gold standard therapy for the treatment of PD. However, long-term use of l-DOPA leads to side effects such as dyskinesias and motor fluctuation. Since purines have neurotransmitter and co-transmitter properties, the function of the purinergic system has been thoroughly studied in the nervous system. Adenosine and adenosine 5′-triphosphate (ATP) are modulators of dopaminergic neurotransmission, neuroinflammatory processes, oxidative stress, excitotoxicity and cell death via purinergic receptor subtypes. Aberrant purinergic receptor signalling can be either the cause or the result of numerous pathological conditions, including neurodegenerative disorders. Many data confirm the involvement of purinergic signalling pathways in PD. Modulation of purinergic receptor subtypes, the activity of ectonucleotidases and ATP transporters could be beneficial in the treatment of PD. We give a brief summary of the background of purinergic signalling focusing on its roles in PD. Possible targets for pharmacological treatment are highlighted.