Main Article Content


A. Mussakhmetov

National Center for Biotechnology,13/5, Korgalzhyn road, Kazakhstan, Nur-Sultan,  010000
 L.N. Gumilyov Eurasian National University, 2 Satpayev str., Kazakhstan, Nur-Sultan, 010008

D. Utepbergenov

Nazarbayev University, Kabanbay batyr ave 53, Kazakhstan, Nur-Sultan, 010000

B. Khassenov, National center for biotechnology

National Center for Biotechnology,13/5, Korgalzhyn road, Kazakhstan, Nur-Sultan,  010000


Parkinson's disease is a progressive age-related neurodegenerative disease, and oxidative stress is an important mediator in its pathogenesis. Loss of neurons in the midbrain region (Substantia nigra) causes dopamine deficiency and leads to the formation of intracellular inclusions containing α-synuclein aggregates. Both of these phenomena are considered neuropathological features of Parkinson's disease. Although the clinical diagnosis is based on the presence of bradykinesia and other major motor signs, Parkinson's disease is associated with many non-motor symptoms that contribute and complicate the disease. The underlying molecular pathogenesis involves several pathways and mechanisms: α-synuclein proteostasis, mitochondrial dysfunction, oxidative stress, disturbances in calcium homeostasis, and neuroinflammation.

Mutations in the PARK7 gene resulting in loss of function of the encoded DJ-1 protein have been identified as the cause of one of several forms of the inherited form of Parkinson's disease. The DJ-1 protein is attributed the role of an antioxidant based on experiments in cellular model systems. The active site of DJ-1 contains a highly reactive cysteine residue (Cys106) which is oxidized under oxidative stress. It is assumed that Cys106 plays a critical role in the biological function of DJ-1, regulating antioxidant protection depending on the oxidation state of Cys106, i.e. acts as a sensor of oxidative stress. Thus, the level of oxidized DJ-1 (oxDJ-1) may serve as a possible biomarker of oxidative stress.


Parkinson's disease, DJ-1, PARK7, neurodegenerative diseases

Article Details


Zaltieri M., Longhena F., Pizzi M., Missale C., Spano P., Bellucci A. (2015) Mitochondrial Dysfunction and alpha-Synuclein Synaptic Pathology in Parkinson's Disease: Who's on First? // Parkinsons Dis. ‒ vol. 2015. ‒ p. 108029.

Dolgacheva L. P., Berezhnov A. V., Fedotova E. I., Zinchenko V. P., Abramov A. Y. (2019) Role of DJ-1 in the mechanism of pathogenesis of Parkinson's disease // J Bioenerg Biomembr.‒ vol. 51, no. 3. ‒ p. 175-188.

Saito Y. (2017)DJ-1 as a Biomarker of Parkinson's Disease // Adv Exp Med Biol. ‒ vol. 1037. ‒ p. 149-171.

Hijioka M., Inden M., Yanagisawa D., Kitamura Y. (2017) DJ-1/PARK7: A New Therapeutic Target for Neurodegenerative Disorders // Biol Pharm Bull.‒ vol. 40, no. 5. ‒ p. 548-552.

Jenner P. (2003)The MPTP-treated primate as a model of motor complications in PD: primate model of motor complications // Neurology. ‒ vol. 61, no. 6 Suppl 3. ‒ p. S4-11.

Ba F., Martin W. R. (2015) Dopamine transporter imaging as a diagnostic tool for parkinsonism and related disorders in clinical practice // Parkinsonism Relat Disord. ‒ vol. 21, no. 2. ‒ p. 87-94.

Kalinderi K., Bostantjopoulou S., Fidani L. (2016) The genetic background of Parkinson's disease: current progress and future prospects // Acta Neurol Scand. ‒ vol. 134, no. 5. ‒ p. 314-326.

Kim C. Y., Alcalay R. N. (2017) Genetic Forms of Parkinson's Disease // Semin Neurol. ‒ vol. 37, no. 2. ‒ p. 135-146.

Kasten M., Hartmann C., Hampf J., Schaake S., Westenberger A., Vollstedt E. J., Balck A., Domingo A., Vulinovic F., Dulovic M., Zorn I., Madoev H., Zehnle H., Lembeck C. M., Schawe L., Reginold J., Huang J., Konig I. R., Bertram L., Marras C., Lohmann K., Lill C. M., Klein C. (2018) Genotype-Phenotype Relations for the Parkinson's Disease Genes Parkin, PINK1, DJ1: MDSGene Systematic Review // Mov Disord. ‒ vol. 33, no. 5. ‒ p. 730-741.

Lola Cook Shukla J. S., Janice Farlow, Nathan D Pankratz, Joanne Wojcieszek, MD, and Tatiana Foroud. (May 25, 2004) Parkinson Disease Overview. GeneReviews.

Poewe W., Seppi K., Tanner C. M., Halliday G. M., Brundin P., Volkmann J., Schrag A. E., Lang A. E. (2017) Parkinson disease // Nat Rev Dis Primers. ‒ vol. 3. ‒ p. 17013.

Thanan R., Oikawa S., Hiraku Y., Ohnishi S., Ma N., Pinlaor S., Yongvanit P., Kawanishi S., Murata M. (2014) Oxidative stress and its significant roles in neurodegenerative diseases and cancer // Int J Mol Sci. ‒ vol. 16, no. 1. ‒ p. 193-217.

Chang K. H., Chen C. M. (2020) The Role of Oxidative Stress in Parkinson's Disease // Antioxidants (Basel). ‒ vol. 9, no. 7.

Monzani E., Nicolis S., Dell'Acqua S., Capucciati A., Bacchella C., Zucca F. A., Mosharov E. V., Sulzer D., Zecca L., Casella L. (2019) Dopamine, Oxidative Stress and Protein-Quinone Modifications in Parkinson's and Other Neurodegenerative Diseases // Angew Chem Int Ed Engl. ‒ vol. 58, no. 20. ‒ p. 6512-6527.

Graves S. M., Xie Z., Stout K. A., Zampese E., Burbulla L. F., Shih J. C., Kondapalli J., Patriarchi T., Tian L., Brichta L., Greengard P., Krainc D., Schumacker P. T., Surmeier D. J. (2020) Dopamine metabolism by a monoamine oxidase mitochondrial shuttle activates the electron transport chain // Nat Neurosci. ‒ vol. 23, no. 1. ‒ p. 15-20.

Nagatsu T., Nagatsu I. (2016)Tyrosine hydroxylase (TH), its cofactor tetrahydrobiopterin (BH4), other catecholamine-related enzymes, and their human genes in relation to the drug and gene therapies of Parkinson's disease (PD): historical overview and future prospects // J Neural Transm (Vienna). ‒ vol. 123, no. 11. ‒ p. 1255-1278.

Zhang S., Wang R., Wang G. (2019) Impact of Dopamine Oxidation on DA-ergic Neurodegeneration // ACS Chem Neurosci. ‒ vol. 10, no. 2. ‒ p. 945-953.

McHugh P. C., Buckley D. A. (2015) The structure and function of the dopamine transporter and its role in CNS diseases // Vitam Horm. ‒ vol. 98. ‒ p. 339-69.

Luk B., Mohammed M., Liu F., Lee F. J. (2015) A Physical Interaction between the Dopamine Transporter and DJ-1 Facilitates Increased Dopamine Reuptake // PLoS One. ‒ vol. 10, no. 8. ‒ p. e0136641.

Mochizuki H., Choong C. J., Baba K. (2020) Parkinson's disease and iron // J Neural Transm (Vienna). ‒ vol. 127, no. 2. ‒ p. 181-187.

Bresgen N., Eckl P. M. (2015) Oxidative stress and the homeodynamics of iron metabolism // Biomolecules. ‒ vol. 5, no. 2. ‒ p. 808-47.

Bertero E., Maack C. (2018) Calcium Signaling and Reactive Oxygen Species in Mitochondria // Circ Res. ‒ vol. 122, no. 10. ‒ p. 1460-1478.

Hurley M. J., Brandon B., Gentleman S. M., Dexter D. T. (2013) Parkinson's disease is associated with altered expression of CaV1 channels and calcium-binding proteins // Brain. ‒ vol. 136, no. Pt 7. ‒ p. 2077-97.

Lautenschlager J., Stephens A. D., Fusco G., Strohl F., Curry N., Zacharopoulou M., Michel C. H., Laine R., Nespovitaya N., Fantham M., Pinotsi D., Zago W., Fraser P., Tandon A., St George-Hyslop P., Rees E., Phillips J. J., De Simone A., Kaminski C. F., Schierle G. S. K. (2018) C-terminal calcium binding of alpha-synuclein modulates synaptic vesicle interaction // Nat Commun. ‒ vol. 9, no. 1. ‒ p. 712.

Kausar S., Wang F., Cui H. (2018) The Role of Mitochondria in Reactive Oxygen Species Generation and Its Implications for Neurodegenerative Diseases // Cells. ‒ vol. 7, no. 12.

Bhat A. H., Dar K. B., Anees S., Zargar M. A., Masood A., Sofi M. A., Ganie S. A. (2015) Oxidative stress, mitochondrial dysfunction and neurodegenerative diseases; a mechanistic insight // Biomed Pharmacother. ‒ vol. 74. ‒ p. 101-10.

Vila M., Przedborski S. (2003) Targeting programmed cell death in neurodegenerative diseases // Nat Rev Neurosci. ‒ vol. 4, no. 5. ‒ p. 365-75.

Keeney P. M., Xie J., Capaldi R. A., Bennett J. P., Jr. (2006) Parkinson's disease brain mitochondrial complex I has oxidatively damaged subunits and is functionally impaired and misassembled // J Neurosci. ‒ vol. 26, no. 19. ‒ p. 5256-64.

Park J., Lee S. B., Lee S., Kim Y., Song S., Kim S., Bae E., Kim J., Shong M., Kim J. M., Chung J. (2006) Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin // Nature. ‒ vol. 441, no. 7097. ‒ p. 1157-61.

Hassanzadeh K., Rahimmi A. (2018) Oxidative stress and neuroinflammation in the story of Parkinson's disease: Could targeting these pathways write a good ending? // J Cell Physiol. ‒ vol. 234, no. 1. ‒ p. 23-32.

Li Q., Barres B. A. (2018) Microglia and macrophages in brain homeostasis and disease // Nat Rev Immunol. ‒ vol. 18, no. 4. ‒ p. 225-242.

Sundal C., Fujioka S., Uitti R. J., Wszolek Z. K. (2012) Autosomal dominant Parkinson's disease // Parkinsonism & Related Disorders. ‒ vol. 18. ‒ p. S7-S10.

Polymeropoulos M. H., Lavedan C., Leroy E., Ide S. E., Dehejia A., Dutra A., Pike B., Root H., Rubenstein J., Boyer R., Stenroos E. S., Chandrasekharappa S., Athanassiadou A., Papapetropoulos T., Johnson W. G., Lazzarini A. M., Duvoisin R. C., Di Iorio G., Golbe L. I., Nussbaum R. L. (1997) Mutation in the alpha-synuclein gene identified in families with Parkinson's disease // Science. ‒ vol. 276, no. 5321. ‒ p. 2045-7.

Kruger R., Kuhn W., Muller T., Woitalla D., Graeber M., Kosel S., Przuntek H., Epplen J. T., Schols L., Riess O. (1998) Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease // Nat Genet. ‒ vol. 18, no. 2. ‒ p. 106-8.

Zarranz J. J., Alegre J., Gomez-Esteban J. C., Lezcano E., Ros R., Ampuero I., Vidal L., Hoenicka J., Rodriguez O., Atares B., Llorens V., Gomez Tortosa E., del Ser T., Munoz D. G., de Yebenes J. G. (2004) The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia // Ann Neurol. ‒ vol. 55, no. 2. ‒ p. 164-73.

Chia S. J., Tan E. K., Chao Y. X. (2020) Historical Perspective: Models of Parkinson's Disease // Int J Mol Sci. ‒ vol. 21, no. 7.

Zimprich A., Biskup S., Leitner P., Lichtner P., Farrer M., Lincoln S., Kachergus J., Hulihan M., Uitti R. J., Calne D. B., Stoessl A. J., Pfeiffer R. F., Patenge N., Carbajal I. C., Vieregge P., Asmus F., Muller-Myhsok B., Dickson D. W., Meitinger T., Strom T. M., Wszolek Z. K., Gasser T. (2004) Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology // Neuron. ‒ vol. 44, no. 4. ‒ p. 601-7.

Cherian A., Divya K. P. (2020) Genetics of Parkinson's disease // Acta Neurol Belg. ‒ vol. 120, no. 6. ‒ p. 1297-1305.

Sidransky E., Nalls M. A., Aasly J. O., Aharon-Peretz J., Annesi G., Barbosa E. R., Bar-Shira A., Berg D., Bras J., Brice A., Chen C. M., Clark L. N., Condroyer C., De Marco E. V., Durr A., Eblan M. J., Fahn S., Farrer M. J., Fung H. C., Gan-Or Z., Gasser T., Gershoni-Baruch R., Giladi N., Griffith A., Gurevich T., Januario C., Kropp P., Lang A. E., Lee-Chen G. J., Lesage S., Marder K., Mata I. F., Mirelman A., Mitsui J., Mizuta I., Nicoletti G., Oliveira C., Ottman R., Orr-Urtreger A., Pereira L. V., Quattrone A., Rogaeva E., Rolfs A., Rosenbaum H., Rozenberg R., Samii A., Samaddar T., Schulte C., Sharma M., Singleton A., Spitz M., Tan E. K., Tayebi N., Toda T., Troiano A. R., Tsuji S., Wittstock M., Wolfsberg T. G., Wu Y. R., Zabetian C. P., Zhao Y., Ziegler S. G. (2009) Multicenter analysis of glucocerebrosidase mutations in Parkinson's disease // N Engl J Med. ‒ vol. 361, no. 17. ‒ p. 1651-61.

Winder-Rhodes S. E., Evans J. R., Ban M., Mason S. L., Williams-Gray C. H., Foltynie T., Duran R., Mencacci N. E., Sawcer S. J., Barker R. A. (2013) Glucocerebrosidase mutations influence the natural history of Parkinson's disease in a community-based incident cohort // Brain. ‒ vol. 136, no Pt 2. ‒ p. 392-9.

Mata I. F., Leverenz J. B., Weintraub D., Trojanowski J. Q., Chen-Plotkin A., Van Deerlin V. M., Ritz B., Rausch R., Factor S. A., Wood-Siverio C., Quinn J. F., Chung K. A., Peterson-Hiller A. L., Goldman J. G., Stebbins G. T., Bernard B., Espay A. J., Revilla F. J., Devoto J., Rosenthal L. S., Dawson T. M., Albert M. S., Tsuang D., Huston H., Yearout D., Hu S. C., Cholerton B. A., Montine T. J., Edwards K. L., Zabetian C. P. (2016) GBA Variants are associated with a distinct pattern of cognitive deficits in Parkinson's disease // Mov Disord. ‒ vol. 31, no. 1. ‒ p. 95-102.

Cilia R., Tunesi S., Marotta G., Cereda E., Siri C., Tesei S., Zecchinelli A. L., Canesi M., Mariani C. B., Meucci N., Sacilotto G., Zini M., Barichella M., Magnani C., Duga S., Asselta R., Solda G., Seresini A., Seia M., Pezzoli G., Goldwurm S. (2016) Survival and dementia in GBA-associated Parkinson's disease: The mutation matters // Ann Neurol. ‒ vol. 80, no. 5. ‒ p. 662-673.

Bonifati V. (2012) Autosomal recessive parkinsonism // Parkinsonism & Related Disorders. ‒ vol. 18. ‒ p. S4-S6.

Kilarski L. L., Pearson J. P., Newsway V., Majounie E., Knipe M. D., Misbahuddin A., Chinnery P. F., Burn D. J., Clarke C. E., Marion M. H., Lewthwaite A. J., Nicholl D. J., Wood N. W., Morrison K. E., Williams-Gray C. H., Evans J. R., Sawcer S. J., Barker R. A., Wickremaratchi M. M., Ben-Shlomo Y., Williams N. M., Morris H. R. (2012) Systematic review and UK-based study of PARK2 (parkin), PINK1, PARK7 (DJ-1) and LRRK2 in early-onset Parkinson's disease // Mov Disord. ‒ vol. 27, no. 12. ‒ p. 1522-9.

Dagda R. K., Pien I., Wang R., Zhu J., Wang K. Z., Callio J., Banerjee T. D., Dagda R. Y., Chu C. T. (2014) Beyond the mitochondrion: cytosolic PINK1 remodels dendrites through protein kinase A // J Neurochem. ‒ vol. 128, no. 6. ‒ p. 864-77.

Camargos S. T., Dornas L. O., Momeni P., Lees A., Hardy J., Singleton A., Cardoso F. (2009) Familial Parkinsonism and early onset Parkinson's disease in a Brazilian movement disorders clinic: phenotypic characterization and frequency of SNCA, PRKN, PINK1, and LRRK2 mutations // Mov Disord. ‒ vol. 24, no. 5. ‒ p. 662-6.

Zhang L., Wang J., Wang J., Yang B., He Q., Weng Q. (2020) Role of DJ-1 in Immune and Inflammatory Diseases // Front Immunol. ‒ vol. 11. ‒ p. 994.

Smith N., Wilson M. A. (2017) Structural Biology of the DJ-1 Superfamily // Adv Exp Med Biol. ‒ vol. 1037. ‒ p. 5-24.

Honbou K., Suzuki N. N., Horiuchi M., Niki T., Taira T., Ariga H., Inagaki F. (2003) The crystal structure of DJ-1, a protein related to male fertility and Parkinson's disease // J Biol Chem. ‒ vol. 278, no 33. ‒ p. 31380-4.

Wilson M. A., Collins J. L., Hod Y., Ringe D., Petsko G. A. (2003) The 1.1-A resolution crystal structure of DJ-1, the protein mutated in autosomal recessive early onset Parkinson's disease // Proc Natl Acad Sci USA. ‒ vol. 100, no. 16. ‒ p. 9256-61.

Lin J., Prahlad J., Wilson M. A. (2012) Conservation of oxidative protein stabilization in an insect homologue of parkinsonism-associated protein DJ-1 // Biochemistry. ‒ vol. 51, no. 18. ‒ p. 3799-807.

Wilson M. A. (2011) The role of cysteine oxidation in DJ-1 function and dysfunction // Antioxid Redox Signal. ‒ vol. 15, no. 1. ‒ p. 111-22.

Ariga H., Takahashi-Niki K., Kato I., Maita H., Niki T., Iguchi-Ariga S. M. (2013) Neuroprotective function of DJ-1 in Parkinson's disease // Oxid Med Cell Longev. ‒ vol. 2013. ‒ p. 683920.

Zhang L., Shimoji M., Thomas B., Moore D. J., Yu S. W., Marupudi N. I., Torp R., Torgner I. A., Ottersen O. P., Dawson T. M., Dawson V. L. (2005) Mitochondrial localization of the Parkinson's disease related protein DJ-1: implications for pathogenesis // Hum Mol Genet. ‒ vol. 14, no. 14. ‒ p. 2063-73.

Junn E., Jang W. H., Zhao X., Jeong B. S., Mouradian M. M. (2009) Mitochondrial localization of DJ-1 leads to enhanced neuroprotection // J Neurosci Res. ‒ vol. 87, no. 1. ‒ p. 123-9.

Li H. M., Niki T., Taira T., Iguchi-Ariga S. M., Ariga H. (2005) Association of DJ-1 with chaperones and enhanced association and colocalization with mitochondrial Hsp70 by oxidative stress // Free Radic Res. ‒ vol. 39, no. 10. ‒ p. 1091-9.

Im J. Y., Lee K. W., Junn E., Mouradian M. M. (2010) DJ-1 protects against oxidative damage by regulating the thioredoxin/ASK1 complex // Neurosci Res. ‒ vol. 67, no. 3. ‒ p. 203-8.

Im J. Y., Lee K. W., Woo J. M., Junn E., Mouradian M. M. (2012) DJ-1 induces thioredoxin 1 expression through the Nrf2 pathway // Hum Mol Genet. ‒ vol. 21, no. 13. ‒ p. 3013-24.

Andreeva A., Bekkhozhin Z., Omertassova N., Baizhumanov T., Yeltay G., Akhmetali M., Toibazar D., Utepbergenov D. (2019) The apparent deglycase activity of DJ-1 results from the conversion of free methylglyoxal present in fast equilibrium with hemithioacetals and hemiaminals // J Biol Chem. ‒ vol. 294, no 49. ‒ p. 18863-18872.

Mihoub M., Abdallah J., Richarme G. (2017) Protein Repair from Glycation by Glyoxals by the DJ-1 Family Maillard Deglycases // Adv Exp Med Biol. ‒ vol. 1037. ‒ p. 133-147.

Heremans I. P., Caligiore F., Gerin I., Bury M., Lutz M., Graff J., Stroobant V., Vertommen D., Teleman A. A., Van Schaftingen E., Bommer G. T. (2022) Parkinson's disease protein PARK7 prevents metabolite and protein damage caused by a glycolytic metabolite // Proc Natl Acad Sci USA. ‒ vol. 119, no 4.