Objective: We investigated whether α-synuclein-derived peptides (recognized specific sequence in α-synuclein) can drive T-cell response and evaluated the neurotoxicity of α-synuclein peptide-specific T-cell in Parkinson’s disease pathogenesis.

Background: Parkinson’s disease (PD) is a neurodegenerative disease characterized by the progressive degeneration of dopaminergic neurons in the midbrain. It is clinically characterized by the progressive degeneration of dopaminergic neurons in substantia nigra pars compacta and motor dysfunctions. Unfortunately, the mechanisms of fundamental progressive neurodegeneration are not exclusively precise; however, several pieces of evidence suggest that immune system dysregulation could play an important role in PD pathogenesis. Abnormal regulation of T cells in the adaptive immune system or to self-antigens could trigger a robust immune reaction and result in uncontrolled inflammation. In recent studies, α-synuclein-specific T cells are increased in PD patients; IL-17-producing T lymphocytes play a critical role in sporadic PD, and other studies demonstrated the association between T-cell gene expression and clinical parameters of PD.

Method: Here, we investigated whether α-synuclein-derived peptide can drive T cell response and evaluated the neurotoxicity of α-Syn peptide-specific T cells. To understand the potential effects of PD pathogenesis-associated T-cell responses, we used PFF and CFA (which is used for the subsequent boosting immune response) + α-synuclein-derived peptides (recognized specific sequence in α-synuclein) immunized mouse model. We examined the autoimmune T cell response after boosting immunization using 5 candidates of α-synuclein-derived peptide in C57BL/6 mice.

Results: The T cell response of immunized mice was assayed after 7 days of boosting immunization. We found behavior deficits, dopaminergic neuronal death, level of dopamine, phosphorylation of α-synuclein (S129 and Y39), neuroinflammation, increased inflammatory cytokines, T-cells infiltration into the brain, and Astro-/Microgliosis as shown in immune activation.

Conclusion: In this study, our data results that T cell response in the autoimmune system associated with α-synuclein pathology could damage dopaminergic neurons as the critical regions of PD; furthermore, it could be the evidence for PD modifying treatments.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-role-of-adaptive-immunity-caused-by-%ce%b1-synuclein-recognition-specific-sequence-peptide-on-the-onset-of-parkinsons-disease-pathogenesis/