Neuroinflammatory Mechanisms in Parkinson's Disease

Parkinson’s disease is marked by progressive loss of dopaminergic neurons in the substantia nigra and widespread accumulation of misfolded α-synuclein. In this setting, neuroinflammation emerges as both a driver and a consequence of neuronal injury. Resident glia—microglia and astrocytes—become chronically activated, releasing pro-inflammatory cytokines, reactive oxygen species and prostaglandins that exacerbate oxidative stress and impair mitochondrial function. Pattern-recognition receptors, such as the receptor for advanced glycation end products, detect aggregated proteins and further amplify inflammatory cascades via p38 mitogen-activated protein kinase and nuclear factor-κB signalling. This sustained immune activation promotes blood–brain barrier dysfunction and peripheral immune cell infiltration, reinforcing a self-perpetuating cycle of neuronal damage. Cyclooxygenase-2-derived prostaglandins contribute to microglial overactivation and synaptic dysfunction, while kinase mediators such as Src tyrosine kinase coordinate inflammatory gene expression. The interplay between protein aggregation, glial activation and vascular changes underlies both motor and non-motor features of the disease. Recognising this, modulation of inflammatory pathways has become a focus for novel therapies, aiming to preserve dopaminergic circuits and maintain neural plasticity. Overall, neuroinflammation in Parkinson’s disease reflects a complex network of cellular and molecular events that link innate immunity to neurodegeneration and offer multiple avenues for intervention.

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Neuroinflammatory Mechanisms in Parkinson's Disease publication trend

The graph below shows the total number of articles in neuroinflammatory mechanisms in parkinson's disease across all publications each year (not limited to Nature Index journals).

Technical terms

Microglia: Innate immune cells of the central nervous system that become activated in response to injury or protein aggregates.

Astrocytes: Star-shaped glial cells that support neuronal metabolism and contribute to inflammatory signalling when activated.

Cytokines: Small proteins released by immune cells that mediate and regulate inflammation and cell communication.

NF-κB: A transcription factor that controls expression of many pro-inflammatory genes once activated.

p38 MAPK: A kinase enzyme that transduces stress and inflammatory signals, leading to cytokine production.

RAGE: Receptor for advanced glycation end products, which binds misfolded proteins and triggers inflammatory pathways.

Src tyrosine kinase: A signalling enzyme involved in the activation of microglia and the expression of inflammatory mediators.

Prostaglandin D2: A lipid mediator produced by cyclooxygenase-2 that amplifies neuroinflammatory responses.

References

1. Selective COX-2 inhibition prevents progressive dopamine neuron degeneration in a rat model of Parkinson's disease. Journal of Neuroinflammation (2004).
2. RAGE Silencing Ameliorates Neuroinflammation by Inhibition of p38-NF-κB Signaling Pathway in Mouse Model of Parkinson’s Disease. Frontiers in Neuroscience (2020).
3. Src Inhibition Attenuates Neuroinflammation and Protects Dopaminergic Neurons in Parkinson’s Disease Models. Frontiers in Neuroscience (2020).
4. Prostaglandin D2/J2 signaling pathway in a rat model of neuroinflammation displaying progressive parkinsonian-like pathology: potential novel therapeutic targets. Journal of Neuroinflammation (2018).