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.
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http://dx.doi.org/10.1186/s12964-025-02136-9 | DOI Listing |
Cell Commun Signal
March 2025
Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, China.
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.
View Article and Find Full Text PDFInt J Mol Sci
October 2024
Department of Chemistry, Tunghai University, No. 1727, Sec. 4, Taiwan Boulevard, Xitun District, Taichung 40704, Taiwan.
DJ-1 is a vital enzyme involved in the maintenance of mitochondrial health, and its mutation has been associated with an increased risk of Parkinson's disease (PD). Effective regulation of DJ-1 activity is essential for the well-being of mitochondria, and DJ-1 is thus a potential target for PD drug development. In this study, two peptides (EEMETIIPVDVMRRA and SRDVVICPDA) were utilized with the aim of enhancing the activity of DJ-1.
View Article and Find Full Text PDFbioRxiv
July 2024
Department of Biochemistry, University of Nebraska, Lincoln, NE 68588.
Antioxidants (Basel)
March 2023
Departamento de Biología Celular y del Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México-UNAM, Ciudad de México 04510, México.
Large-size subunit catalases (LSCs) have an additional C-terminal domain (CT) that is structurally similar to Hsp31 and DJ-1 proteins, which have molecular chaperone activity. The CT of LSCs derives from a bacterial Hsp31 protein. There are two CT dimers with inverted symmetry in LSCs, one dimer in each pole of the homotetrameric structure.
View Article and Find Full Text PDFAntioxidants (Basel)
May 2022
Departamento de Biología Celular y del Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, UNAM, Mexico City 04510, Mexico.
Bacterial and fungal large-size subunit catalases (LSCs) are like small-size subunit catalases (SSCs) but have an additional C-terminal domain (CT). The catalytic domain is conserved at both primary sequence and structural levels and its amino acid composition is optimized to select HO over water. The CT is structurally conserved, has an amino acid composition similar to very stable proteins, confers high stability to LSCs, and has independent molecular chaperone activity.
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