Mini Review - Journal of Neurology and Neurorehabilitation Research (2025) Volume 10, Issue 1

The Role of Neuroinflammation in the Progression of Parkinson�s Diseas

Department of Neurosciences, Kerala University of Health Sciences, India.

*Corresponding Author:

Rajesh Menon
Department of Neurosciences
Kerala University of Health Sciences, India.
E-mail: sophie.laurent@biodiv.umontpellier.fr

Received: 03-Jan-2025, Manuscript No. JNNR-25-169091; Editor assigned: 04-Jan-2025, PreQC No. JNNR-25-1690915(PQ); Reviewed: 18-Jan-2025, QC No JNNR-25-1690915; Revised: 21-Jan-2025, Manuscript No. JNNR-25-1690915(R); Published: 28-Jan-2025, DOI:10.35841/aajnnr-10.1.242

Citation: Menon R. The role of neuroinflammation in the progression of parkinson’s disease. J Neurol Neurorehab Res. 2025;10(1):242.

Introduction

Parkinson’s disease is a progressive neurodegenerative disorder that primarily affects motor function, characterized by symptoms such as bradykinesia, resting tremor, rigidity, and postural instability. It is also associated with non-motor symptoms, including cognitive decline, mood disturbances, autonomic dysfunction, and sleep disorders, which can significantly impair quality of life. The pathological hallmark of Parkinson’s disease is the selective degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to dopamine depletion in the striatum. Another defining feature is the accumulation of intracellular protein aggregates composed primarily of misfolded alpha-synuclein, forming Lewy bodies and Lewy neurites. Although the precise mechanisms underlying neuronal loss remain incompletely understood, increasing evidence implicates neuroinflammation as a central contributor to disease onset and progression. Far from being a mere consequence of neuronal injury, neuroinflammation appears to play an active role in amplifying and perpetuating neurodegenerative processes in Parkinson’s disease [1].

Neuroinflammation refers to the activation of the brain’s innate immune system, primarily mediated by microglia, astrocytes, and other immune-related components. In a healthy brain, microglia remain in a surveillant, “resting” state, constantly monitoring the neural environment for signs of injury or infection. Upon detecting danger signals such as misfolded proteins, damaged neurons, or pathogen-associated molecules, they transform into an activated state, releasing a range of inflammatory mediators, including cytokines, chemokines, and reactive oxygen species. This acute inflammatory response is intended to protect neural tissue by clearing harmful agents and promoting repair. However, in Parkinson’s disease, the inflammatory response becomes chronic and dysregulated, leading to a self-perpetuating cycle of neuronal damage and further immune activation. This persistent inflammatory environment contributes to the progressive loss of dopaminergic neurons and exacerbates the spread of pathological alpha-synuclein [2].

Post-mortem studies of Parkinson’s disease brains consistently reveal evidence of sustained microglial activation, particularly in the substantia nigra. Activated microglia in these regions exhibit morphological changes, increased expression of major histocompatibility complex class II molecules, and elevated production of pro-inflammatory cytokines such as tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6. These molecules, while beneficial in acute injury contexts, can become neurotoxic when chronically elevated. They disrupt neuronal function, impair synaptic signaling, and contribute to oxidative stress, which is particularly harmful to dopaminergic neurons due to their high metabolic demand and vulnerability to oxidative damage. Oxidative stress not only damages neuronal membranes, proteins, and DNA but also promotes further aggregation of alpha-synuclein, creating additional stimuli for microglial activation [3].

Astrocytes, another key glial cell type, also participate in the inflammatory milieu of Parkinson’s disease. Under normal conditions, astrocytes support neuronal health by maintaining extracellular ion balance, recycling neurotransmitters, and providing metabolic support. In the diseased brain, astrocytes can adopt a reactive phenotype, releasing both neuroprotective and neurotoxic factors. While some astrocytic responses may attempt to shield neurons from injury, chronic reactive astrocytosis in Parkinson’s disease appears to contribute to neuronal demise by releasing pro-inflammatory mediators, reducing trophic support, and impairing glutamate uptake, which can lead to excitotoxicity. The interplay between activated microglia and reactive astrocytes creates a potent inflammatory network that sustains neurodegeneration [4].

The role of neuroinflammation in Parkinson’s disease is further underscored by the involvement of the peripheral immune system. Peripheral immune cells, including T lymphocytes, have been detected infiltrating the brains of Parkinson’s disease patients, suggesting that the blood-brain barrier becomes compromised during the disease process. This infiltration may amplify neuroinflammation by introducing additional immune mediators and cytotoxic activity into the central nervous system. Certain subsets of T cells, particularly pro-inflammatory CD4+ T helper cells, have been implicated in promoting microglial activation and neuronal injury, whereas regulatory T cells, which normally suppress excessive immune responses, appear to be reduced or functionally impaired in Parkinson’s disease. This imbalance between pro-inflammatory and anti-inflammatory immune influences may accelerate neurodegeneration [5].

Conclusion

In conclusion, neuroinflammation plays a central and active role in the progression of Parkinson’s disease, contributing to the degeneration of dopaminergic neurons through a complex interplay of microglial activation, astrocytic dysfunction, peripheral immune infiltration, oxidative stress, and alpha-synuclein pathology. Rather than being a secondary phenomenon, inflammation appears to drive disease processes and amplify neuronal injury, establishing a self-perpetuating cycle of degeneration. Genetic and environmental factors modulate the intensity of this inflammatory response, influencing disease susceptibility and progression rate. Understanding the precise mechanisms by which neuroinflammation interacts with other pathological features of Parkinson’s disease will be essential for developing targeted, effective therapies. Efforts to modulate harmful inflammatory pathways while preserving protective immune functions hold promise for slowing or halting disease progression, offering hope for improved outcomes in this debilitating disorder. Continued research in this area, integrating clinical observations, experimental models, and biomarker development, will be vital to translating these insights into meaningful therapeutic advances for individuals living with Parkinson’s disease.

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