Dopaminergic Modulation of Immune Response in Neurological Disorders

The interplay between dopaminergic signalling and immune function has emerged as a critical factor in the onset and progression of a range of neurological disorders. Beyond its classical role as a neurotransmitter in motor control and cognition, dopamine influences cytokine release, immune-cell activation and phagocytic activity within the central nervous system and periphery. In conditions such as Parkinson’s disease and ischaemic stroke, depletion of dopamine in key circuits correlates with heightened microglial reactivity and infiltration of peripheral leucocytes. Activation of D1-like receptors often promotes anti-inflammatory cascades via cyclic AMP, whereas engagement of D2-like receptors can suppress pro-inflammatory NF-κB signalling by recruiting regulatory proteins. Modulation of dopamine uptake through the dopamine transporter further shapes systemic immune tone. Dysregulation of these pathways not only exacerbates neuronal injury but also impairs reparative processes. Consequently, pharmacological targeting of dopamine receptors or transporter activity offers promising routes to rebalance neuroinflammation and protect vulnerable neuronal populations.

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Dopaminergic Modulation of Immune Response in Neurological Disorders publication trend

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Technical terms

Dopamine transporter (DAT): Membrane protein responsible for reabsorbing extracellular dopamine into presynaptic and peripheral immune cells.

Dopamine receptors (D1-like and D2-like): Families of G-protein-coupled receptors that mediate excitatory or inhibitory dopaminergic signals in neurons and immune cells.

Regulatory T cells (Tregs): Subset of CD4+ lymphocytes that suppress excessive immune activation and maintain self-tolerance.

Cytokine: Soluble signalling protein released by immune cells to coordinate inflammatory and anti-inflammatory responses.

Microglia: Resident macrophage-like cells in the central nervous system that survey the environment and clear debris.

Phagocytosis: Process by which immune cells engulf and digest pathogens or cellular debris.

Striatonigral pathway: Neural circuit connecting the striatum to the substantia nigra, crucial for regulating movement and vulnerable in degenerative disorders.

References

1. Neuroprotective effect of L-DOPA-induced interleukin-13 on striatonigral degeneration in cerebral ischemia. Cell Death & Disease (2024).
2. Treating activated regulatory T cells with pramipexole protects human dopaminergic neurons from 6‐OHDA‐induced degeneration. CNS Neuroscience & Therapeutics (2024).
3. Who Knew? Dopamine Transporter Activity Is Critical in Innate and Adaptive Immune Responses. Cells (2023).