Parkinson's disease is a neurodegenerative disorder marked by the degeneration of
dopaminergic neurons and clinical symptoms such as tremors, rigidity, and slowed movements.
A key feature of Parkinson's disease is the accumulation of misfolded alpha-synuclein,
forming insoluble Lewy bodies in the substantia nigra pars compacta, which contributes
to neurodegeneration. These alpha-synuclein aggregates may act as autoantigens, leading
to T-cell-mediated neuroinflammation and contributing to dopaminergic cell death.
Our perspective explores the hypothesis that Parkinson's disease may have an autoimmune
component, highlighting research that connects peripheral immune responses with neurodegeneration.
T cells derived from Parkinson's disease patients appear to have the potential to
initiate an autoimmune response against alpha-synuclein and its modified peptides,
possibly leading to the formation of neo-epitopes. Recent evidence associates Parkinson's
disease with abnormal immune responses, as indicated by increased levels of immune
cells, such as CD4+ and CD8+ T cells, observed in both patients and mouse models.
The convergence of T cells filtration increasing major histocompatibility complex
molecules, and the susceptibility of dopaminergic neurons supports the hypothesis
that Parkinson's disease may exhibit autoimmune characteristics. Understanding the
immune mechanisms involved in Parkinson's disease will be crucial for developing therapeutic
strategies that target the autoimmune aspects of the disease. Novel approaches, including
precision medicine based on major histocompatibility complex/human leukocyte antigen
typing and early biomarker identification, could pave the way for immune-based treatments
aimed at slowing or halting disease progression. This perspective explores the relationship
between autoimmunity and Parkinson's disease, suggesting that further research could
deepen understanding and offer new therapeutic avenues. In this paper, it is organized
to provide a comprehensive perspective on the autoimmune aspects of Parkinson's disease.
It investigates critical areas such as the autoimmune response observed in Parkinson's
disease patients and the role of autoimmune mechanisms targeting alpha-synuclein in
Parkinson's disease. The paper also examines the impact of CD4+ T cells, specifically
Th1 and Th17, on neurons through in vitro and ex vivo studies. Additionally, it explores
how alpha-synuclein influences glia-induced neuroinflammation in Parkinson's disease.
The discussion extends to the clinical implications and therapeutic landscape, offering
insights into potential treatments. Consequently, we aim to provide a comprehensive
perspective on the autoimmune aspects of Parkinson's disease, incorporating both supportive
and opposing views on its classification as an autoimmune disorder and exploring implications
for clinical applications.
