Lewy Body Formation through the lens of Cytokine-Mediated Neuroinflammation in Parkinson's Disease Development

Abstract

Abstract Background: Understanding inflammation's role in Parkinson's disease (PD) is crucial for uncovering therapeutic targets and improving patient outcomes. Inflammatory cytokines like TNF-alpha, IL-1β, IL-6, IL-12, IL-18, IL-23, IL-33, IFN-γ, and TNF-β contribute to neurodegeneration. Insights into inflammation's mechanisms may lead to disease-modifying treatments, aid in diagnosing PD, and inform the study of other neurodegenerative disorders. This study seeks to elucidate inflammation's impact on PD pathogenesis and identify potential therapeutic interventions. Methods: A comprehensive search encompassing databases such as PubMed, MEDLINE, Google Scholar, open access / subscription-based journals, was conducted to retrieve relevant articles for the investigation of the involvement of pro-inflammatory cytokines in neuroinflammation and their impact on Parkinson's disease (PD) development in relation to Lewy Body formation. Articles were searched without any date restrictions. Utilizing the criteria delineated in the methodology section, studies were systematically reviewed to elucidate the relationship between pro-inflammatory cytokines and Parkinson's disease progression. This study adheres to relevant PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Results: Dysregulation of inflammatory cytokines TNF-alpha, IL-1β, IL-6, IL-12, IL-18, IL-23, IL-33, IFN-γ, and TNF-β occurs in Parkinson's disease (PD). These cytokines contribute to neuroinflammation, disrupting neuronal homeostasis and promoting α-synuclein aggregation, leading to Lewy body formation. Activation of microglia and astrocytes initiates a cascade of events, including oxidative stress, mitochondrial dysfunction, and impaired protein clearance mechanisms. This cascade results in neuronal damage and dysfunction characteristic of PD. This study points to potential crosstalk between inflammatory pathways and α-synuclein pathology, further exacerbating neurodegeneration. Overall, the results underscore the critical role of inflammation in PD pathogenesis, highlighting the need for targeted anti-inflammatory therapies to mitigate neurodegeneration and alleviate PD symptoms. Conclusion: Inflammation involving TNF-alpha, IL-1β, IL-6, IL-12, IL-18, IL-23, IL-33, IFN-γ, and TNF-β disrupts neuronal homeostasis, fostering Lewy body formation in Parkinson's disease. Activation of microglia and astrocytes triggers neuroinflammation, exacerbating oxidative stress, mitochondrial dysfunction, and protein clearance impairment. This cascade of events leads to neuronal damage and α-synuclein aggregation. Consequently, PD symptoms arise from neuronal dysfunction and degeneration. Targeting cytokine-mediated inflammation offers a potential therapeutic strategy for PD, necessitating further research into its mechanistic intricacies.