Decoding Parkinson Disorder (PD) Pathophysiology: α-Synuclein over-expression enhances inward calcium influx and exosome release in LUHMES cells.

The hall-mark events for Parkinsons Disorder (PD) are Lewy Body (LB) formation and further degeneration of midbrain dopaminergic neurons. Even though α-Synuclein (SNCA) is established as key molecular component of LBs, yet there is no clear understanding of pathophysiological mechanisms acting behind the scene. In such scenario we failed to comprehensively demonstrate the exact reasons behind PD pathology seeding and its spread. Several mechanisms are proposed for PD pathology seeding and spreading and among these the transfer of pathological SNCA via exosomal/extracellular vesicles release is also advocated.We performedpatch-clamp electrophysiology recordings on fetal human mesencephalic cell line (LUHMES, Lund human mesencephalic); a mimiced model cell system of dopaminergic neurons in vitro . Voltage clamp recordings from SNCA overexpressing LUHMES cells accounts for an altered morphology, enhanced inward Ica and membrane capacitance ( Cm ). NTA results suggested us a higher particle concentration for the size range between 50-150 nm, correspondingto the size of exosomes.