Dopaminergic regulation of inflammation and immunity in Parkinson's disease: friend or foe?

Parkinson's disease (PD) is a neurodegenerative disease affecting 7-10 million people worldwide. Currently, there is no treatment available to prevent or delay PD progression, partially due to the limited understanding of the pathological events which lead to the death of dopaminergic neurons in the substantia nigra in the brain, which is known to be the cause of PD symptoms. The current available treatments aim at compensating dopamine (DA) deficiency in the brain using its precursor levodopa, dopaminergic agonists and some indirect dopaminergic agents. The immune system is emerging as a critical player in PD. Therefore, immune-based approaches have recently been proposed to be used as potential antiparkinsonian agents. It has been well-known that dopaminergic pathways play a significant role in regulating immune responses in the brain. Although dopaminergic agents are the primary antiparkinsonian treatments, their immune regulatory effect has yet to be fully understood. The present review summarises the current available evidence of the immune regulatory effects of DA and its mimics and discusses dopaminergic agents as antiparkinsonian drugs. Based on the current understanding of their involvement in the regulation of neuroinflammation in PD, we propose that targeting immune pathways involved in PD pathology could offer a better treatment outcome for PD patients. The present review aims to collect and critically summarise available evidence regarding the immune effects of dopamine and their mimics and to put dopaminergic agents used as antiparkinsonian drugs in the perspective of current knowledge about the involvement of immunity and inflammation in Parkinson's disease (PD). Dopamine and dopaminergic agonists may exert both anti- and proinflammatory effects in the periphery and the brain and unravelling their immunomodulating potential would possibly help to exploit their full therapeutic efficacy in PD and provide novel insights into PD pathogenesis and how to modify disease progression acting on immune mechanisms effectively.image

Automated summary

Parkinson's disease is a neurodegenerative disease with no available treatment options that can effectively delay its progression. The immune system has been identified as playing a critical role in this disease, suggesting that immune-based approaches may hold potential as antiparkinsonian agents. Dopaminergic pathways are known to regulate immune responses, but the full extent of the immune regulatory effects of dopaminergic agents is not yet fully understood.