DJ-1 Protein and Its Role in the Development of Parkinson’s Disease: Studies on Experimental Models

• Published in: Biochemistry (Moscow) 2021-06, Vol.86 (6), p.627-640
• Main Authors: Buneeva, Olga A., Medvedev, Alexey E.
• Format: Article
• Language: English
• Subjects: Amino acid sequence; Amino acids; Analysis; Animals; ATP synthase; Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Catalytic activity; Cell culture; Cell death; Compartments; Dimerization; Dimers; Enzymes; Life Sciences; Low molecular weights; Medical research; Medicine, Experimental; Microbiology; Mitochondria; Molecular weight; Monomers; Movement disorders; Neurodegenerative diseases; Neuroprotection; Neurotoxins; Oxidative stress; PARK7 protein; Parkinson's disease; Proteins; Review; Tat protein; Toxins
• ISSN: 0006-2979; 1608-3040
• DOI: 10.1134/S000629792106002X

DJ-1, also known as Parkinson’s disease protein 7, is a multifunctional protein ubiquitously expressed in cells and tissues. Interacting with proteins of various intracellular compartments, DJ-1 plays an important role in maintaining different cellular functions. Mutant DJ-1 forms containing amino acid substitutions (especially L166P), typical of Parkinson’s disease, are characterized by impaired dimerization, stability, and folding. DJ-1 exhibits several types of catalytic activity; however, in the enzyme classification it exists as protein deglycase (EC 3.5.1.124). Apparently, in different cell compartments DJ-1 exhibits catalytic and non-catalytic functions, and their ratio still remains unknown. Oxidative stress promotes dissociation of cytoplasmic DJ-1 dimers into monomers, which are translocated to the nucleus, where this protein acts as a coactivator of various signaling pathways, preventing cell death. In mitochondria, DJ-1 is found in the synthasome, where it interacts with the β ATP synthase subunit. Downregulation of the DJ-1 gene under conditions of experimental PD increases sensitivity of the cells to neurotoxins, and introduction of the recombinant DJ-1 protein attenuates manifestation of this pathology. The thirteen-membered fragment of the DJ-1 amino acid sequence attached to the heptapeptide of the TAT protein penetrating into the cells exhibited neuroprotective properties in various PD models both in cell cultures and after administration to animals. Low molecular weight DJ-1 ligands also demonstrate therapeutic potential, providing neuroprotective effects seen during their incubation with cells and administration to animals.