T- Cell Responses Against Alpha-synuclein in Parkinson's Disease

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease in the elderly after Alzheimer’s disease (AD). There is a lot of resemblance between AD and PD in the mechanism of proteinaceous aggregation intra and extracellularly. PD is a subtype of synucleinopathies whereas a-synuclein (a-syn) is the main element of aggregation. Neuroinflammation is considered as one of the main driving factors that accelerate a-syn aggregation. Therefore, adaptive immune cells such as T cells are natural responders to such inflammation as many studies have shown that these cells selectively infiltrate the affected regions in the brain. However, the role of the adaptive immune cells, particularly T cells, in PD is not well understood. Herein, we found that the strongest T-cell response against ?-syn-derived peptides arose from the region that encompasses amino acids between (36-77). Phosphorylated and native forms of different single peptides were compared, and the results suggested that phosphorylation at S129 and Y125 enhance T-cell response, while phosphorylation is not necessarily for Y39 and S87 to enhance the immune response. Furthermore, PBMC characterization showed a significant increase in FoxP3+Helios- T regulatory cells (Tregs) in overall CD4+ T cells subset as well as in CD4+CD25+ T cells subset in PD patients. Interestingly, a significant increase in TIM3 immune checkpoint (IC) in PD patients was observed as opposed to other ICs such as PD-1, CTLA4 and LAG3 that did not show any difference compared to healthy controls. These findings may complement immunotherapy by suggesting a specific region/peptide as a target for vaccination. Moreover, differential expression of certain ICs or the increase in a certain population may represent a potential biomarker, identify an underlying pathophysiological mechanism for PD or provide new means of therapy.