Age-Related Increase in Caveolin-1 Expression Facilitates Cell-To-Cell Transmission of α-Synuclein in Neurons
Abstract Background: Parkinson's disease (PD) is the second most prevalent neurodegenerative disease, with aging being considered the greatest risk factor for developing PD. Caveolin-1 (Cav-1) is known to participate in the aging process. Recent evidence indicates that prion-like propagation of misfolded α-synuclein (α-syn) released from neurons to neighboring neurons plays an important role in PD progression. In the present study, we explored the association between cav-1 and cell-to-cell transmission of α-syn.Methods: Using SH-SY5Y cells and primary neurons overexpressing WT and Y14A cav-1, we investigated the effect of cav-1 expression on the uptake of α-syn using a dual chamber system. Additionally, we investigated the effect of cav-1 expression on the formation of Lewy body-like inclusions using co-culture assay and microfluidic chamber assay.Results: We demonstrated that cav-1 expression in the brain increased with age, and considerably increased in the brain of A53T α-syn transgenic mice. Cav-1 overexpression facilitated the uptake of α-syn into neurons and formation of additional Lewy body-like inclusion bodies, phosphorylation of cav-1 at tyrosine 14 was found to be crucial for this process. Conclusions: This study demonstrates the relationship between age and α-syn spread and will facilitate our understanding of the molecular mechanism of the cell-to-cell transmission of α-syn.