Significance of Cell Membrane Repair in Parkinson's Disease

Abstract

Objective: Parkinson’s disease (PD) is the second most common neurodegenerative disorder and affects an estimated 10 million people worldwide. PD pathogenesis involves the death of neuronal cells due to the breakdown of their cell membranes. Membrane repair is a mechanism that appears in nearly every eukaryotic cell that repairs disruptions in the plasma membrane to maintain cell health and function. The aim of the present study was to determine the if compromised membrane repair can contribute to the progression of PD. Materials and Methods: Using a glass bead mechanical damage assay, we injured N2A neuroblastoma cells with three different conditions: GFP transfected control cells, cells expressing alpha synuclein, and cells expressing A53T, an alpha synuclein mutant linked to PD. We then measured the amount of an intracellular enzyme, lactase dehydrogenase (LDH), that was released from the cells after injury with glass beads to determine how well the membrane repaired. (n=16) We also injured the membrane of these cells with a laser injury heat damage assay. In this mechanism, a laser is used to injure the cells, and influx of FM4-64 dye into the cell is measured to determine the rate of membrane repair. (n=60) Results: In the mechanical damage assay, cells expressing alpha synuclein released more LDH, which suggests that membrane repair may be compromised in PD. In the laser damage assay, cells expressing alpha synuclein showed significantly more FM4-64 dye influx. We observed increased dye influx in WT Alpha Synuclein cells. This shows that Alpha Synuclein transfected cells do not repair as effectively as control cells when exposed to the same conditions. These findings support that membrane repair may be compromised in PD. Elucidating that membrane repair is impaired in PD leads us to investigate if existing membrane repair enhancing agents could be potential therapeutics for the disease. American Physiological Society Summer Undergraduate Research Fellowship (APS SURF) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.