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

Abstract

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.

Intruders or protectors – the multifaceted role of B cells in CNS disorders

“…Parkinson’s disease (PD) is characterized by death of dopaminergic neurons in the substantia nigra, resulting in dysregulation of movements including bradykinesia, tremor and rigidity ( Furgiuele et al, 2023 ). Lewy bodies accumulate composed of inappropriately folded α-synuclein, which aggregate within neurons, further contributing to neuronal death and pathogenesis.…”

Exploring Parkinson’s Disease-Associated Depression: Role of Inflammation on the Noradrenergic and Serotonergic Pathways

“…Neuroinflammation is one of the most critical complications of PD linked to protein aggregates, oxidative stress, neurodegeneration itself, and peripheral immune and inflammatory changes. Although the cause-effect mechanisms remain unclear, neuronal loss in PD is undoubtedly associated with chronic inflammation, which is mediated mainly by microglia and, to a lesser extent, by astrocytes and oligodendrocytes [24,25].…”

“…Reactive microglia secrete many pro-inflammatory cytokines such as interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin 1-β (IL-1β), IL-6, and upregulates enzymes such as inducible nitric oxide synthase (iNOS) and cyclooxygenase 1 and 2 (COX-1/COX-2) [25,26]. Notwithstanding, activated microglia in PD have been associated with different PD-related genes/proteins like SNCA and LRRK2.…”

“…On the other hand, peripheral D1R activation was associated with increased nuclear transcription factor nuclear factor kappa b (NF-κB) and NLRP3 inflammasome, with a consequent increase in IL-6, IL-1β, and IL-18 levels. These controversial data could be related to species variation in immune-related pathways, dopamine receptor expression, as well as differences in used dopamine concentrations [25].…”