AUTHOR=Salas-Leal Alma C. , Salas-Pacheco Sergio M. , Hernández-Cosaín Erik I. , Vélez-Vélez Lilia M. , Antuna-Salcido Elizabeth I. , Castellanos-Juárez Francisco X. , Méndez-Hernández Edna M. , Llave-León Osmel La , Quiñones-Canales Gerardo , Arias-Carrión Oscar , Sandoval-Carrillo Ada A. , Salas-Pacheco José M. 

TITLE=Differential expression of PSMC4, SKP1, and HSPA8 in Parkinson’s disease: insights from a Mexican mestizo population

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=16

YEAR=2023

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2023.1298560

DOI=10.3389/fnmol.2023.1298560

ISSN=1662-5099

ABSTRACT=<p>Parkinson’s disease (PD) is a complex neurodegenerative condition characterized by alpha-synuclein aggregation and dysfunctional protein degradation pathways. This study investigates the differential gene expression of pivotal components (<italic>UBE2K</italic>, <italic>PSMC4</italic>, <italic>SKP1</italic>, and <italic>HSPA8</italic>) within these pathways in a Mexican-Mestizo PD population compared to healthy controls. We enrolled 87 PD patients and 87 controls, assessing their gene expression levels via RT-qPCR. Our results reveal a significant downregulation of <italic>PSMC4</italic>, <italic>SKP1</italic>, and <italic>HSPA8</italic> in the PD group (<italic>p</italic> = 0.033, <italic>p</italic> = 0.003, and <italic>p</italic> = 0.002, respectively). Logistic regression analyses establish a strong association between PD and reduced expression of <italic>PSMC4</italic>, <italic>SKP1</italic>, and <italic>HSPA8</italic> (OR = 0.640, 95% CI = 0.415–0.987; OR = 0.000, 95% CI = 0.000–0.075; OR = 0.550, 95% CI = 0.368–0.823, respectively). Conversely, <italic>UBE2K</italic> exhibited no significant association or expression difference between the groups. Furthermore, we develop a gene expression model based on <italic>HSPA8</italic>, <italic>PSMC4</italic>, and <italic>SKP1</italic>, demonstrating robust discrimination between healthy controls and PD patients. Notably, the model’s diagnostic efficacy is particularly pronounced in early-stage PD. In conclusion, our study provides compelling evidence linking decreased gene expression of <italic>PSMC4</italic>, <italic>SKP1</italic>, and <italic>HSPA8</italic> to PD in the Mexican-Mestizo population. Additionally, our gene expression model exhibits promise as a diagnostic tool, particularly for early-stage PD diagnosis.</p>