Neuroinflammation and Dopaminergic Neurodegeneration in Parkinson's Disease

Parkinson’s disease is characterised by the progressive loss of nigrostriatal dopaminergic neurons, leading to motor symptoms such as bradykinesia, rigidity and tremor, and a spectrum of non-motor manifestations. A growing body of research implicates chronic neuroinflammation as both a driver and amplifier of neuronal demise. Activation of microglia and astrocytes within the substantia nigra pars compacta releases pro-inflammatory cytokines, reactive oxygen and nitrogen species, and degradative enzymes, which exacerbate α-synuclein aggregation and compromise neuronal viability. Peripheral inflammatory signals—triggered by gut dysbiosis or systemic endotoxins—can breach the blood–brain barrier, prime central immune cells and perpetuate a feed-forward cycle of neurodegeneration. Deciphering the mechanisms that link innate immunity to dopaminergic cell loss holds promise for disease-modifying therapies that target inflammatory pathways and preserve motor function.

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Neuroinflammation and Dopaminergic Neurodegeneration in Parkinson's Disease publication trend

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

Technical terms

Neuroinflammation: Activation of the brain’s innate immune response, often mediated by microglia and astrocytes, resulting in release of cytokines and reactive species.

Microglia: Resident immune cells of the central nervous system that monitor the neuronal environment and produce inflammatory mediators when activated.

Dopaminergic neuron: A nerve cell that synthesises and releases dopamine, particularly vulnerable in Parkinson’s disease and localised in the substantia nigra.

Substantia nigra pars compacta (SNpc): A midbrain region rich in dopaminergic neurons critically involved in movement control and selectively degenerated in Parkinson’s disease.

Lipopolysaccharide (LPS): A bacterial endotoxin commonly used experimentally to provoke systemic or central inflammatory responses.

α-Synuclein: A neuronal protein prone to misfolding and aggregation, forming Lewy bodies that are pathological hallmarks of Parkinson’s disease.

References

1. Animal models of Parkinson’s disease: bridging the gap between disease hallmarks and research questions. Translational Neurodegeneration (2023).
2. Systemic inflammation accelerates neurodegeneration in a rat model of Parkinson’s disease overexpressing human alpha synuclein. npj Parkinson's Disease (2024).
3. Activation of HCA2 regulates microglial responses to alleviate neurodegeneration in LPS-induced in vivo and in vitro models. Journal of Neuroinflammation (2023).