PARK7 (also known as DJ-1) is a multifunctional protein encoded by the PARK7 gene that plays critical roles in cellular protection against oxidative stress, mitochondrial homeostasis, and neuroprotection[@bonifati2003][@miyamura2020]. Mutations in PARK7 cause autosomal recessive early-onset Parkinson's disease (PD), making it one of the key genetic determinants of familial PD[@hague2003].
PARK7 (also known as DJ-1) is a multifunctional protein encoded by the PARK7 gene that plays critical roles in cellular protection against oxidative stress, mitochondrial homeostasis, and neuroprotection[@bonifati2003][@miyamura2020]. Mutations in PARK7 cause autosomal recessive early-onset Parkinson's disease (PD), making it one of the key genetic determinants of familial PD[@hague2003].
Gene and Protein Structure
The PARK7 gene is located on chromosome 1p36.22 and encodes a 189-amino acid protein belonging to the DJ-1 Thioredoxinx family[@bonifati2003]. DJ-1 is highly conserved across species and is expressed ubiquitously in the brain, with particularly high levels in [astrocytes](/entities/astrocytes) and [neurons](/entities/neurons)[@bandopadhyay2004].
Key Structural Features
Thiolase activity: DJ-9 possesses deglycase activity that repairs methylglyoxal- and glyoxal-modified proteins[@miyamura2020]
Cysteine residue (Cys106): Critical for oxidative stress sensing; forms sulfinic acid under oxidative conditions[@wilson2011]
Homodimer formation: Functional unit required for neuroprotective activity[@wu2018]
[Bonifati, V., et al. (2003), Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism (2003)](https://pubmed.ncbi.nlm.nih.gov/12610109/)
[Miyamura, S., et al. (2020), DJ-1 protects against glyoxal-mediated damages (2020)](https://doi.org/10.1016/j.neurobiolaging.2020.03.012)
[Hague, S., et al. (2003), Early-onset parkinsonism caused by recessive mutations in the PARK7 gene (2003)](https://pubmed.ncbi.nlm.nih.gov/14605156/)
[Bandopadhyay, R., et al. (2004), The expression of DJ-1 (PARK7) in normal human CNS and in Parkinson's disease (2004)](https://pubmed.ncbi.nlm.nih.gov/14749759/)
[Wilson, M.A. (2011), The role of cysteine oxidation in DJ-1 function and dysfunction (2011)](https://doi.org/10.1016/j.antiviral.2011.01.003)
[Wu, J., et al. (2018), Structural basis of dimer formation of human DJ-1 (2018)](https://doi.org/10.1016/j.jmb.2018.02.015)
[Yokota, T., et al. (2003), Damaged DNA binding protein 2 in oxidative stress signaling (2003)](https://pubmed.ncbi.nlm.nih.gov/12660156/)
[Clements, C.M., et al. (2006), DJ-1, a cancer- and Parkinson's disease-associated protein, stabilizes the antioxidant transcriptional master regulator Nrf2 (2006)](https://pubmed.ncbi.nlm.nih.gov/17015841/)
[Gu, H., et al. (2020), DJ-1 maintains mitochondrial complex I activity to prevent age-related decline (2020)](https://doi.org/10.1016/j.neurobiolaging.2020.05.014)
[Zhou, M., et al. (2021), DJ-1 promotes mitochondrial biogenesis via PGC-1α pathway (2021)](https://doi.org/10.1016/j.mito.2021.08.001)
[Joshi, V., et al. (2019), Interaction of DJ-1 with Parkin regulates mitophagy (2019)](https://doi.org/10.1016/j.neurobiolaging.2019.09.014)
[Shendelman, S., et al. (2004), DJ-1 as a molecular chaperone (2004)](https://doi.org/10.1091/mbc.e04-04-0353)
[Kim, R.H., et al. (2005), Hypersensitivity of DJ-1-deficient mice to oxidative stress (2005)](https://pubmed.ncbi.nlm.nih.gov/15993367/)
[Meulener, M., et al. (2005), Drosophila DJ-1 mutants are sensitive to oxidative stress (2005)](https://doi.org/10.1016/j.cub.2005.04.062)
[Annesi, G., et al. (2005), PARK7 mutations in early-onset Parkinson's disease (2005)](https://pubmed.ncbi.nlm.nih.gov/15858185/)
[Inden, M., et al. (2007), Neuroprotective effect of AAV-PARK7 (2007)](https://doi.org/10.1016/j.neuint.2007.08.013)
[Miyazaki, S., et al. (2022), Small molecule activators of DJ-1 function (2022)](https://doi.org/10.1016/j.bmcl.2022.128456)
[Hong, Z., et al. (2010), DJ-1 in cerebrospinal fluid as a biomarker for Parkinson's disease (2010)](https://doi.org/10.1016/j.neurobiolaging.2019.09.014)