Pathophysiology and Treatment of Parkinson's Disease

Parkinson’s disease is a progressive neurodegenerative disorder characterised chiefly by the loss of nigrostriatal dopaminergic neurons and the accumulation of misfolded α-synuclein into Lewy bodies. Mitochondrial dysfunction, oxidative stress and neuroinflammatory responses contribute to neuronal vulnerability, while impaired proteostasis disrupts synaptic integrity across multiple brain regions. Clinically, the disease manifests with bradykinesia, rigidity and resting tremor, often accompanied by non-motor features such as sleep disturbance, cognitive decline and autonomic dysfunction. Symptomatic treatment remains centred on dopamine replacement therapies, notably levodopa and dopamine agonists, alongside deep brain stimulation for refractory motor fluctuations. Emerging strategies aim to modify disease progression through mitochondrial stabilisers, immunotherapies targeting α-synuclein, gene-based approaches, and cell replacement techniques. Rehabilitation, dietary intervention and neuromodulation are increasingly recognised for their role in preserving function and quality of life.

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Pathophysiology and Treatment of Parkinson's Disease publication trend

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

Technical terms

Nigrostriatal pathway: The dopaminergic projection from the substantia nigra to the striatum essential for voluntary movement control.

α-Synuclein: A presynaptic protein prone to misfolding and aggregation, forming Lewy bodies that characterise Parkinson’s pathology.

Dopaminergic neuron: A nerve cell that synthesises and releases dopamine, critical for motor and reward pathways.

Threshold theory: A model positing that neurological symptoms appear when synaptic network reserves fall below a critical level.

GABAergic neurotransmission: Inhibitory signalling mediated by γ-aminobutyric acid, which modulates neuronal excitability and network stability.

Prodromal stage: An early phase of disease during which non-motor symptoms or subtle biomarkers emerge before classical motor signs.

Biomarker: A measurable indicator of biological or pathological processes, used for diagnosis, prognosis or monitoring.

References

1. Neuronal threshold functions: Determining symptom onset in neurological disorders. Progress in Neurobiology (2024).
2. Sleep disorders cause Parkinson's disease or the reverse is true: Good GABA good night. CNS Neuroscience & Therapeutics (2024).
3. Searching for Biomarkers in the Blood of Patients at Risk of Developing Parkinson’s Disease at the Prodromal Stage. International Journal of Molecular Sciences (2023).
4. Pathophysiology of Motor Dysfunction in Parkinson’s Disease as the Rationale for Drug Treatment and Rehabilitation. Parkinson's Disease (2016).