Neuroprotective role and mechanistic insights of DJ-1 dimerization in Parkinson's disease.

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder primarily driven by the degeneration of dopaminergic neurons, with limited therapeutic interventions currently available. Among the critical factors in PD pathogenesis, DJ-1, a multifunctional protein, has emerged as a key neuroprotective agent against oxidative stress-a major contributor to the disease. Recent research has emphasized the pivotal role of DJ-1 dimerization in enhancing its neuroprotective capabilities. This review provides an in-depth analysis of the molecular mechanisms underlying DJ-1 dimerization and its relevance to PD. Specifically, we specifically explore how dimerization stabilizes DJ-1, enhances its antioxidative properties, improves mitochondrial function, and modulates key cellular pathways essential for neuronal survival. Furthermore, we discuss the molecular determinants governing DJ-1 dimerization, highlighting its potential both as a biomarker for PD diagnosis and a promising therapeutic target. By synthesizing current advancements, we propose that targeting DJ-1 dimerization may offer innovative strategies to slow PD progression and bolster neuronal health. This review positions DJ-1 as a central focus in PD research, paving the way for future studies aimed at developing neuroprotective therapies.