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Cited by 254Parkinson's Disease Mechanisms and TreatmentsNuclear Receptors and SignalingGenomics, phytochemicals, and oxidative stress

Role of DJ-1 in the mechanism of pathogenesis of Parkinson's disease

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Dolgacheva, Ludmila P., Berezhnov, Alexey V., Fedotova, Evgeniya I., Zinchenko, Valery P., Abramov, Andrey Y.·2019·Journal of Bioenergetics and Biomembranes
DOI 10.1007/s10863-019-09798-4PMC PMC6531411
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Abstract

DJ-1 protein has multiple specific mechanisms to protect dopaminergic neurons against neurodegeneration in Parkinson's disease. Wild type DJ-1 can acts as oxidative stress sensor and as an antioxidant. DJ-1 exhibits the properties of molecular chaperone, protease, glyoxalase, transcriptional regulator that protects mitochondria from oxidative stress. DJ-1 increases the expression of two mitochondrial uncoupling proteins (UCP 4 and UCP5), that decrease mitochondrial membrane potential and leads to the suppression of ROS production, optimizes of a number of mitochondrial functions, and is regarded as protection for the neuronal cell survival. We discuss also the stabilizing interaction of DJ-1 with the mitochondrial Bcl-xL protein, which regulates the activity of (Inositol trisphosphate receptor) IP 3 R, prevents the cytochrome c release from mitochondria and inhibits the apoptosis activation. Upon oxidative stress DJ-1 is able to regulate various transcription factors including nuclear factor Nrf2, PI3K/PKB, and p53 signal pathways. Stress-activated transcription factor Nrf2 regulates the pathways to protect cells against oxidative stress and metabolic pathways initiating the NADPH and ATP production. DJ-1 induces the Nrf2 dissociation from its inhibitor Keap1 (Kelch-like ECH-associated protein 1), promoting Nrf2 nuclear translocation and binding to antioxidant response elements. DJ-1 is shown to be a co-activator of the transcription factor NF-kB. Under nitrosative stress, DJ-1 may regulate PI3K/PKB signaling through PTEN transnitrosylation, which leads to inhibition of phosphatase activity. DJ-1 has a complex modulating effect on the p53 pathway: one side DJ-1 directly binds to p53 to restore its transcriptional activity and on the other hand DJ-1 can stimulate deacylation and suppress p53 transcriptional activity. The ability of the DJ-1 to induce activation of different transcriptional factors and change redox balance protect neurons against aggregation of α-synuclein and oligomer-induced neurodegeneration.

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  • Redox metabolism-associated genes PINK1 and PARK7 were upregulated in Ts21 OPCs and Oligos.

    “We identified redox metabolism-associated genes upregulated in Ts21 OPCs and Oligos - PINK1 and PARK7 - that have been implicated in cellular senescence and neurodegenerative diseases (49, 50) (Fig. 5G).”

    From Molecular and cellular processes disrupted in the early postnatal Down syndrome prefrontal cortex (2026) · cites this paper as [50]

    The Introduction links both PINK1 and DJ-1 (PARK7) to Parkinson’s disease, and the paper discusses DJ-1’s role in oxidative-stress responses. It does not establish a role for these genes in cellular senescence. The Ts21 upregulation is presented as the citing authors’ own finding, not as a finding attributed to this source. (LLM, conf=0.85)

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Cited by

Sorted by citations

Authors
Dolgacheva, L. P., Berezhnov, A. V., Fedotova, E. I., Zinchenko, V. P., & Abramov, A. Y.
Affiliations
  • Institute of Cell Biophysics (RU)
  • UCL Queen Square Institute of Neurology (GB)
Corresponding author
Abramov, Andrey Y.
ORCID
Venue
Journal of Bioenergetics and Biomembranes
Publisher
Springer Science and Business Media LLC
Published
2019-05-03
Volume
51
Issue
3
Pages
175-188
ISSN
  • 0145-479X (ISSN-L)
  • 1573-6881
DOI
10.1007/s10863-019-09798-4
PMC
PMC6531411
OpenAlex
W2943359597
Cited by
254
References
12
Citations by year
2026: 29 · 2025: 39 · 2024: 29 · 2023: 37 · 2022: 49 · 2021: 46 · 2020: 19 · 2019: 6
FWCI
4.04
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Bioenergetics and Biomembranes (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
University College London
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
Keywords
DJ-1, Parkinson's disease, oxidative stress, dopaminergic neurons, mitochondrial dysfunction, UCP4, UCP5, Bcl-xL, IP3 receptor, cytochrome c release, apoptosis, Nrf2, Keap1, p53, NF-kB, nitrosative stress, redox homeostasis, alpha-synuclein aggregation, neuroprotection
MeSH terms
Protein Deglycase DJ-1, Animals, Humans, Mitochondria, Nerve Tissue Proteins, Parkinson Disease, Transcription Factors, Signal Transduction, Membrane Potential, Mitochondrial, Dopaminergic Neurons

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