Irina Petrenko, “The Role of TMEM175 in PD Neurodegeneration”
Mentor: An-Phu Tran, Biological Sciences, Letters & Science (College of)
Poster #151
Parkinson’s disease (PD) is the second most common neurodegenerative disorder and the fastest-growing brain disease globally. It is influenced by both genetic and environmental factors, with gene mutations accounting for up to 20% of cases. Genome-wide association studies (GWAS) have identified over 90 loci that may influence PD risk, many of which are involved in endolysosomal pathways. Among the genetic contributors, variants in the TMEM175 gene, which encodes lysosomal potassium channel 175, have been strongly associated with PD risk. In cells, TMEM175 plays a crucial role in maintaining lysosomal pH balance, and its dysfunction has been linked to disruptions in autophagy and the accumulation of α-synuclein, both hallmarks of PD pathology. However, the mechanisms through which TMEM175 deficiency leads to neuronal degeneration remain unclear. Recent studies suggest that TMEM175 may also modulate mitochondrial function and oxidative stress responses, potentially through its involvement in NADPH-dependent pathways. In this study, we aim to explore how TMEM175 depletion affects lysosomal stability and oxidative stress in human cells. We first established optimal culture conditions for HEK293 cells and performed TMEM175 knockdown in these cells using small interfering RNA (siRNA). The efficiency of TMEM175 knockdown is currently being assessed using RT-PCR. Future experiments will employ immunocytochemistry and Western blot analysis to evaluate the impact of siRNA-mediated TMEM175 knockdown on endolysosomal trafficking, NADPH homeostasis, and autophagic processes. By identifying the mechanisms through which TMEM175 influences PD pathogenesis, our findings may provide new insights into potential therapeutic strategies for the disease.