Prkn

Summary

Gene Symbol: Prkn
Description: parkin RBR E3 ubiquitin protein ligase
Alias: Park, Park2, E3 ubiquitin-protein ligase parkin, Parkinson disease (autosomal recessive, juvenile) 2, parkin, parkin RBR E3 ubiquitin protein ligase 2, parkin variant SV5DEL, parkinson protein 2, E3 ubiquitin protein ligase
Species: rat
Products:     Prkn

Top Publications

  1. Ren Y, Zhao J, Feng J. Parkin binds to alpha/beta tubulin and increases their ubiquitination and degradation. J Neurosci. 2003;23:3316-24 pubmed
    ..Its ability to enhance the ubiquitination and degradation of misfolded tubulins may play a significant role in protecting neurons from toxins that cause PD. ..
  2. Sun X, Liu J, Crary J, Malagelada C, Sulzer D, Greene L, et al. ATF4 protects against neuronal death in cellular Parkinson's disease models by maintaining levels of parkin. J Neurosci. 2013;33:2398-407 pubmed publisher
    ..Finally, parkin silencing blocked the protective capacity of ATF4. These results indicate that ATF4 plays a protective role in PD through the regulation of parkin. ..
  3. Chen D, Gao F, Li B, Wang H, Xu Y, Zhu C, et al. Parkin mono-ubiquitinates Bcl-2 and regulates autophagy. J Biol Chem. 2010;285:38214-23 pubmed publisher
    ..Moreover, overexpression of parkin enhances the interactions between Bcl-2 and Beclin 1. Our results provide evidence that parkin mono-ubiquitinates Bcl-2 and regulates autophagy via Bcl-2. ..
  4. Itier J, Ibanez P, Mena M, Abbas N, Cohen Salmon C, Bohme G, et al. Parkin gene inactivation alters behaviour and dopamine neurotransmission in the mouse. Hum Mol Genet. 2003;12:2277-91 pubmed
  5. Imai Y, Soda M, Hatakeyama S, Akagi T, Hashikawa T, Nakayama K, et al. CHIP is associated with Parkin, a gene responsible for familial Parkinson's disease, and enhances its ubiquitin ligase activity. Mol Cell. 2002;10:55-67 pubmed
    ..Furthermore, CHIP enhanced the ability of Parkin to inhibit cell death induced by Pael-R. Taken together, these results indicate that CHIP is a mammalian E4-like molecule that positively regulates Parkin E3 activity. ..
  6. Narendra D, Tanaka A, Suen D, Youle R. Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol. 2008;183:795-803 pubmed publisher
    Loss-of-function mutations in Park2, the gene coding for the ubiquitin ligase Parkin, are a significant cause of early onset Parkinson's disease...
  7. Hebron M, Lonskaya I, Sharpe K, Weerasinghe P, Algarzae N, Shekoyan A, et al. Parkin ubiquitinates Tar-DNA binding protein-43 (TDP-43) and promotes its cytosolic accumulation via interaction with histone deacetylase 6 (HDAC6). J Biol Chem. 2013;288:4103-15 pubmed publisher
    ..Parkin and TDP-43 formed a multiprotein complex with HDAC6, perhaps to mediate TDP-43 translocation. In conclusion, Parkin ubiquitinates TDP-43 and facilitates its cytosolic accumulation through a multiprotein complex with HDAC6. ..
  8. Joch M, Ase A, Chen C, MacDonald P, Kontogiannea M, Corera A, et al. Parkin-mediated monoubiquitination of the PDZ protein PICK1 regulates the activity of acid-sensing ion channels. Mol Biol Cell. 2007;18:3105-18 pubmed
  9. Fallon L, Moreau F, Croft B, Labib N, Gu W, Fon E. Parkin and CASK/LIN-2 associate via a PDZ-mediated interaction and are co-localized in lipid rafts and postsynaptic densities in brain. J Biol Chem. 2002;277:486-91 pubmed
    ..These data implicate for the first time a PDZ-mediated interaction between parkin and CASK in neurodegeneration and possibly in ubiquitination of proteins involved in synaptic transmission and plasticity. ..

More Information

Publications76

  1. Wenzel D, Lissounov A, Brzovic P, Klevit R. UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids. Nature. 2011;474:105-8 pubmed publisher
    ..UBCH7 exhibits activity with the RING-in-between-RING (RBR) family of E3s that includes parkin (also known as PARK2) and human homologue of ariadne (HHARI; also known as ARIH1)...
  2. Ko H, Lee Y, Shin J, Karuppagounder S, Gadad B, Koleske A, et al. Phosphorylation by the c-Abl protein tyrosine kinase inhibits parkin's ubiquitination and protective function. Proc Natl Acad Sci U S A. 2010;107:16691-6 pubmed publisher
    Mutations in PARK2/Parkin, which encodes a ubiquitin E3 ligase, cause autosomal recessive Parkinson disease (PD)...
  3. Trempe J, Sauvé V, Grenier K, Seirafi M, Tang M, Ménade M, et al. Structure of parkin reveals mechanisms for ubiquitin ligase activation. Science. 2013;340:1451-5 pubmed publisher
    Mutations in the PARK2 (parkin) gene are responsible for an autosomal recessive form of Parkinson's disease. The parkin protein is a RING-in-between-RING E3 ubiquitin ligase that exhibits low basal activity...
  4. Helton T, Otsuka T, Lee M, Mu Y, Ehlers M. Pruning and loss of excitatory synapses by the parkin ubiquitin ligase. Proc Natl Acad Sci U S A. 2008;105:19492-7 pubmed publisher
    Mutations in the PARK2 gene cause hereditary Parkinson disease (PD). The PARK2 gene product, termed parkin, is an E3 ubiquitin ligase that mediates the transfer of ubiquitin onto diverse substrate proteins...
  5. Zhang Y, Gao J, Chung K, Huang H, Dawson V, Dawson T. Parkin functions as an E2-dependent ubiquitin- protein ligase and promotes the degradation of the synaptic vesicle-associated protein, CDCrel-1. Proc Natl Acad Sci U S A. 2000;97:13354-9 pubmed
    ..The loss of Parkin's ubiquitin-protein ligase function in familial-linked mutations suggests that this may be the cause of familial autosomal recessive Parkinson's disease. ..
  6. Shin J, Ko H, Kang H, Lee Y, Lee Y, Pletinkova O, et al. PARIS (ZNF746) repression of PGC-1? contributes to neurodegeneration in Parkinson's disease. Cell. 2011;144:689-702 pubmed publisher
    ..The identification of PARIS provides a molecular mechanism for neurodegeneration due to parkin inactivation. ..
  7. Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, et al. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature. 1998;392:605-8 pubmed
    ..Mutations in the newly identified gene appear to be responsible for the pathogenesis of AR-JP, and we have therefore named the protein product 'Parkin'. ..
  8. Vercammen L, Van der Perren A, Vaudano E, Gijsbers R, Debyser Z, Van den Haute C, et al. Parkin protects against neurotoxicity in the 6-hydroxydopamine rat model for Parkinson's disease. Mol Ther. 2006;14:716-23 pubmed
    Loss-of-function mutations in the PARK2 gene are the major cause of early onset familial Parkinson's disease. The gene product, parkin, is an E3 ligase of the ubiquitin-proteasome pathway involved in protein degradation...
  9. Perez F, Palmiter R. Parkin-deficient mice are not a robust model of parkinsonism. Proc Natl Acad Sci U S A. 2005;102:2174-9 pubmed
    ..To determine whether mutations in the mouse parkin gene (Park2) also result in a parkinsonian phenotype, we generated mice with a targeted deletion of parkin exon 2...
  10. Imai Y, Soda M, Takahashi R. Parkin suppresses unfolded protein stress-induced cell death through its E3 ubiquitin-protein ligase activity. J Biol Chem. 2000;275:35661-4 pubmed
  11. Schlossmacher M, Frosch M, Gai W, Medina M, Sharma N, Forno L, et al. Parkin localizes to the Lewy bodies of Parkinson disease and dementia with Lewy bodies. Am J Pathol. 2002;160:1655-67 pubmed
    ..These results suggest that functional parkin proteins may be required during LB formation. ..
  12. Mouatt Prigent A, Muriel M, Gu W, El Hachimi K, Lücking C, Brice A, et al. Ultrastructural localization of parkin in the rat brainstem, thalamus and basal ganglia. J Neural Transm (Vienna). 2004;111:1209-18 pubmed
    ..In HS22 cells over-expressing parkin, the distribution of the protein was similar to that observed in the perikarya of the labeled neurons. ..
  13. Rakovic A, Shurkewitsch K, Seibler P, Grünewald A, Zanon A, Hagenah J, et al. Phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1)-dependent ubiquitination of endogenous Parkin attenuates mitophagy: study in human primary fibroblasts and induced pluripotent stem cell-derived neurons. J Biol Chem. 2013;288:2223-37 pubmed publisher
    ..Taken together, our data demonstrate that mitophagy differs between human non-neuronal and neuronal cells and between "endogenous" and "Parkin-overexpressing" cellular models. ..
  14. Kalia S, Lee S, Smith P, Liu L, Crocker S, Thorarinsdottir T, et al. BAG5 inhibits parkin and enhances dopaminergic neuron degeneration. Neuron. 2004;44:931-45 pubmed
    ..This contrasts with the antideath functions ascribed to BAG family members and suggests a potential role for BAG5 in promoting neurodegeneration in sporadic PD through its functional interactions with parkin and Hsp70. ..
  15. Imai Y, Soda M, Inoue H, Hattori N, Mizuno Y, Takahashi R. An unfolded putative transmembrane polypeptide, which can lead to endoplasmic reticulum stress, is a substrate of Parkin. Cell. 2001;105:891-902 pubmed
    ..Moreover, the insoluble form of Pael receptor accumulates in the brains of AR-JP patients. Here, we show that the unfolded Pael receptor is a substrate of Parkin, the accumulation of which may cause selective neuronal death in AR-JP. ..
  16. Trempe J, Chen C, Grenier K, Camacho E, Kozlov G, McPherson P, et al. SH3 domains from a subset of BAR proteins define a Ubl-binding domain and implicate parkin in synaptic ubiquitination. Mol Cell. 2009;36:1034-47 pubmed publisher
    ..The NMR structure of the Ubl-SH3 complex identifies the PaRK extension, a unique C-terminal motif in the parkin Ubl required for SH3 binding and for parkin-mediated ..
  17. Foroud T, Uniacke S, Liu L, Pankratz N, Rudolph A, Halter C, et al. Heterozygosity for a mutation in the parkin gene leads to later onset Parkinson disease. Neurology. 2003;60:796-801 pubmed
    ..In addition, the clinical findings of parkin-positive individuals are remarkably similar to those without mutations. ..
  18. Van Humbeeck C, Cornelissen T, Hofkens H, Mandemakers W, Gevaert K, De Strooper B, et al. Parkin interacts with Ambra1 to induce mitophagy. J Neurosci. 2011;31:10249-61 pubmed publisher
    ..These data identify interaction of Parkin with Ambra1 as a key mechanism for induction of the final clearance step of Parkin-mediated mitophagy. ..
  19. Chaugule V, Burchell L, Barber K, Sidhu A, Leslie S, Shaw G, et al. Autoregulation of Parkin activity through its ubiquitin-like domain. EMBO J. 2011;30:2853-67 pubmed publisher
    ..Our observations provide important molecular insights into the underlying basis of Parkinson's disease, and in the regulation of RBR E3-ligase activity. ..
  20. LaVoie M, Ostaszewski B, Weihofen A, Schlossmacher M, Selkoe D. Dopamine covalently modifies and functionally inactivates parkin. Nat Med. 2005;11:1214-21 pubmed
    Inherited mutations in PARK2, the gene encoding parkin, cause selective degeneration of catecholaminergic neurons in the substantia nigra and locus coeruleus of the brainstem, resulting in early-onset parkinsonism...
  21. Gegg M, Cooper J, Chau K, Rojo M, Schapira A, Taanman J. Mitofusin 1 and mitofusin 2 are ubiquitinated in a PINK1/parkin-dependent manner upon induction of mitophagy. Hum Mol Genet. 2010;19:4861-70 pubmed publisher
    ..PINK1 and parkin are thus required for the removal of damaged mitochondria in dopaminergic cells, and inhibition of this pathway may lead to the accumulation of defective mitochondria which may contribute to PD pathogenesis. ..
  22. Goldberg M, Fleming S, Palacino J, Cepeda C, Lam H, Bhatnagar A, et al. Parkin-deficient mice exhibit nigrostriatal deficits but not loss of dopaminergic neurons. J Biol Chem. 2003;278:43628-35 pubmed
    ..Together these findings provide the first evidence for a novel role of parkin in dopamine regulation and nigrostriatal function, and a non-essential role of parkin in the survival of nigral neurons in mice. ..
  23. Huynh D, Nguyen D, Pulst Korenberg J, Brice A, Pulst S. Parkin is an E3 ubiquitin-ligase for normal and mutant ataxin-2 and prevents ataxin-2-induced cell death. Exp Neurol. 2007;203:531-41 pubmed
    ..The role of parkin variants in modifying the SCA2 phenotype and its use as a therapeutic target should be further investigated. ..
  24. Yao D, Gu Z, Nakamura T, Shi Z, Ma Y, Gaston B, et al. Nitrosative stress linked to sporadic Parkinson's disease: S-nitrosylation of parkin regulates its E3 ubiquitin ligase activity. Proc Natl Acad Sci U S A. 2004;101:10810-4 pubmed
    ..These findings may thus provide a molecular link between free radical toxicity and protein accumulation in sporadic Parkinson's disease. ..
  25. Palacino J, Sagi D, Goldberg M, Krauss S, Motz C, Wacker M, et al. Mitochondrial dysfunction and oxidative damage in parkin-deficient mice. J Biol Chem. 2004;279:18614-22 pubmed
  26. Staropoli J, McDermott C, Martinat C, Schulman B, Demireva E, Abeliovich A. Parkin is a component of an SCF-like ubiquitin ligase complex and protects postmitotic neurons from kainate excitotoxicity. Neuron. 2003;37:735-49 pubmed
    ..Furthermore, parkin overexpression attenuates the accumulation of cyclin E in toxin-treated primary neurons, including midbrain dopamine neurons, and protects them from apoptosis. ..
  27. Avraham E, Rott R, Liani E, Szargel R, Engelender S. Phosphorylation of Parkin by the cyclin-dependent kinase 5 at the linker region modulates its ubiquitin-ligase activity and aggregation. J Biol Chem. 2007;282:12842-50 pubmed
    ..Phosphorylation by Cdk5 may contribute to the accumulation of toxic Parkin substrates and decrease the ability of dopaminergic cells to cope with toxic insults in Parkinson disease. ..
  28. Kuroda Y, Mitsui T, Kunishige M, Matsumoto T. Parkin affects mitochondrial function and apoptosis in neuronal and myogenic cells. Biochem Biophys Res Commun. 2006;348:787-93 pubmed
    ..The present results suggest the cell-selective function of parkin, i.e., parkin possesses anti-apoptotic and anti-oxidant function in neuronal or myogenic cells but not in kidney cells. ..
  29. Smith W, Pei Z, Jiang H, Moore D, Liang Y, West A, et al. Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin, and mutant LRRK2 induces neuronal degeneration. Proc Natl Acad Sci U S A. 2005;102:18676-81 pubmed
  30. Um J, Min D, Rhim H, Kim J, Paik S, Chung K. Parkin ubiquitinates and promotes the degradation of RanBP2. J Biol Chem. 2006;281:3595-603 pubmed
    ..Our findings suggested that the intracellular levels of RanBP2 and its functional activity may be modulated by Parkin-mediated ubiquitination and proteasomal pathways. ..
  31. Dachsel J, Lücking C, Deeg S, Schultz E, Lalowski M, Casademunt E, et al. Parkin interacts with the proteasome subunit alpha4. FEBS Lett. 2005;579:3913-9 pubmed
    ..Full-length parkin and parkin lacking the N-terminal ubiquitin-like domain slightly increased the proteasomal activity in HEK 293T cells, in line with the latter hypothesis. ..
  32. Lim K, Chew K, Tan J, Wang C, Chung K, Zhang Y, et al. Parkin mediates nonclassical, proteasomal-independent ubiquitination of synphilin-1: implications for Lewy body formation. J Neurosci. 2005;25:2002-9 pubmed
    ..Our results suggest that parkin is a dual-function ubiquitin ligase and that K63-linked ubiquitination of synphilin-1 by parkin may be involved in the formation of Lewy body inclusions associated with PD. ..
  33. Jiang H, Ren Y, Yuen E, Zhong P, Ghaedi M, Hu Z, et al. Parkin controls dopamine utilization in human midbrain dopaminergic neurons derived from induced pluripotent stem cells. Nat Commun. 2012;3:668 pubmed publisher
    ..Thus, the study provides novel targets and a physiologically relevant screening platform for disease-modifying therapies of PD. ..
  34. Henn I, Bouman L, Schlehe J, Schlierf A, Schramm J, Wegener E, et al. Parkin mediates neuroprotection through activation of IkappaB kinase/nuclear factor-kappaB signaling. J Neurosci. 2007;27:1868-78 pubmed
    ..Thus, our results support a direct link between the neuroprotective activity of parkin and ubiquitin signaling in the IKK/NF-kappaB pathway. ..
  35. LaVoie M, Cortese G, Ostaszewski B, Schlossmacher M. The effects of oxidative stress on parkin and other E3 ligases. J Neurochem. 2007;103:2354-68 pubmed
  36. Song P, Trajkovic K, Tsunemi T, Krainc D. Parkin Modulates Endosomal Organization and Function of the Endo-Lysosomal Pathway. J Neurosci. 2016;36:2425-37 pubmed publisher
    Mutations in PARK2 (parkin), which encodes Parkin protein, an E3 ubiquitin ligase, are associated with autosomal recessive early-onset Parkinson's disease (PD)...
  37. Dagda R, Cherra S, Kulich S, Tandon A, Park D, Chu C. Loss of PINK1 function promotes mitophagy through effects on oxidative stress and mitochondrial fission. J Biol Chem. 2009;284:13843-55 pubmed publisher
    ..Furthermore, PINK1 and Parkin may cooperate through different mechanisms to maintain mitochondrial homeostasis. ..
  38. Ciechanover A, Brundin P. The ubiquitin proteasome system in neurodegenerative diseases: sometimes the chicken, sometimes the egg. Neuron. 2003;40:427-46 pubmed
    ..This raises hopes for a better understanding of the pathogenetic mechanisms involved in these diseases and for the development of novel, mechanism-based therapeutic modalities. ..
  39. Feng Y, Zhao J, Hou H, Zhang H, Jiao Y, Wang J, et al. WDR26 promotes mitophagy of cardiomyocytes induced by hypoxia through Parkin translocation. Acta Biochim Biophys Sin (Shanghai). 2016;48:1075-1084 pubmed
    ..This study provides novel insights into the protective role of WDR26 in cardiomyocyte injury during hypoxia. WDR26 may serve as a potential target for the treatment of myocardial ischemia. ..
  40. Gu W, Abbas N, Lagunes M, Parent A, Pradier L, Bohme G, et al. Cloning of rat parkin cDNA and distribution of parkin in rat brain. J Neurochem. 2000;74:1773-6 pubmed
    ..Thus, the role of parkin may be much more global than previously thought on the basis of genetic findings gathered in cases of early-onset parkinsonism. ..
  41. Hristova V, Beasley S, Rylett R, Shaw G. Identification of a novel Zn2+-binding domain in the autosomal recessive juvenile Parkinson-related E3 ligase parkin. J Biol Chem. 2009;284:14978-86 pubmed publisher
    Missense mutations in park2, encoding the parkin protein, account for approximately 50% of autosomal recessive juvenile Parkinson disease (ARJP) cases...
  42. Moszczynska A, Saleh J, Zhang H, Vukusic B, Lee F, Liu F. Parkin disrupts the alpha-synuclein/dopamine transporter interaction: consequences toward dopamine-induced toxicity. J Mol Neurosci. 2007;32:217-27 pubmed
    ..Moreover, we have found that parkin protects against DA-induced cell toxicity in dopaminergic SK-N-SH cells. These findings will help identify the role of these proteins in the etiology and/or maintenance of Parkinson's disease. ..
  43. Dong Z, Ferger B, Paterna J, Vogel D, Furler S, Osinde M, et al. Dopamine-dependent neurodegeneration in rats induced by viral vector-mediated overexpression of the parkin target protein, CDCrel-1. Proc Natl Acad Sci U S A. 2003;100:12438-43 pubmed
    ..These results show that CDCrel-1 overexpression exerts dopamine-dependent neurotoxicity and suggest that inhibition of dopamine secretion by CDCrel-1 may contribute to the development of AR-JP. ..
  44. Zhuang J, Wen X, Zhang Y, Shan Q, Zhang Z, Zheng G, et al. TDP-43 upregulation mediated by the NLRP3 inflammasome induces cognitive impairment in 2 2',4,4'-tetrabromodiphenyl ether (BDE-47)-treated mice. Brain Behav Immun. 2017;65:99-110 pubmed publisher
  45. Humbert J, Beyer K, Carrato C, Mate J, Ferrer I, Ariza A. Parkin and synphilin-1 isoform expression changes in Lewy body diseases. Neurobiol Dis. 2007;26:681-7 pubmed
    ..These findings suggest that parkin and synphilin-1 isoform expression changes play a significant role in the pathogenesis of LB diseases. ..
  46. Bai J, Safadi S, Mercier P, Barber K, Shaw G. Ataxin-3 is a multivalent ligand for the parkin Ubl domain. Biochemistry. 2013;52:7369-76 pubmed publisher
  47. Hunn B, Cragg S, Bolam J, Spillantini M, Wade Martins R. Impaired intracellular trafficking defines early Parkinson's disease. Trends Neurosci. 2015;38:178-88 pubmed publisher
    ..Dysfunction of the dopaminergic synapse heralds trafficking impairment. ..
  48. Scarffe L, Stevens D, Dawson V, Dawson T. Parkin and PINK1: much more than mitophagy. Trends Neurosci. 2014;37:315-24 pubmed publisher
    ..Recent work has focused on the role of PINK1 and parkin in mediating mitochondrial autophagy (mitophagy); however, emerging evidence casts parkin and PINK1 as key players in multiple domains of mitochondrial health and quality control...
  49. Zhang X, Yuan D, Sun Q, Xu L, Lee E, Lewis A, et al. Calcium/calmodulin-dependent protein kinase regulates the PINK1/Parkin and DJ-1 pathways of mitophagy during sepsis. FASEB J. 2017;31:4382-4395 pubmed publisher
    ..Zhang, X., Yuan, D., Sun, Q., Xu, L., Lee, E., Lewis, A. J., Zuckerbraun, B. S., Rosengart, M. R. Calcium/calmodulin-dependent protein kinase regulates the PINK1/Parkin and DJ-1 pathways of mitophagy during sepsis. ..
  50. McLelland G, Soubannier V, Chen C, McBride H, Fon E. Parkin and PINK1 function in a vesicular trafficking pathway regulating mitochondrial quality control. EMBO J. 2014;33:282-95 pubmed publisher
  51. Han K, Hassanzadeh S, Singh K, Menazza S, Nguyen T, Stevens M, et al. Parkin regulation of CHOP modulates susceptibility to cardiac endoplasmic reticulum stress. Sci Rep. 2017;7:2093 pubmed publisher
    ..Additionally, Parkin is identified as a novel post-translational regulatory moderator of CHOP stability and uncovers an additional stress-modifying function of this E3-ubiquitin ligase. ..
  52. Kubo S, Kitami T, Noda S, Shimura H, Uchiyama Y, Asakawa S, et al. Parkin is associated with cellular vesicles. J Neurochem. 2001;78:42-54 pubmed
    ..We demonstrated the ability of parkin to bind to the membranes through a broad region except for the ubiquitin-like domain. The significance of SV localization of parkin is discussed. ..
  53. D Amico A, Maugeri G, Reitano R, Cavallaro S, D Agata V. Proteomic Analysis of Parkin Isoforms Expression in Different Rat Brain Areas. Protein J. 2016;35:354-362 pubmed
    b>PARK2 gene's mutations are related to the familial form of juvenile Parkinsonism, also known as the autosomic recessive juvenile Parkinsonism. This gene encodes for parkin, a 465-amino acid protein...
  54. Kang J, Hong J, Lee S. Melatonin enhances mitophagy and mitochondrial biogenesis in rats with carbon tetrachloride-induced liver fibrosis. J Pineal Res. 2016;60:383-93 pubmed publisher
    ..These results suggest that melatonin protects against liver fibrosis via upregulation of mitophagy and mitochondrial biogenesis, and may be useful as an anti-fibrotic treatment. ..
  55. Romaní Aumedes J, Canal M, Martín Flores N, Sun X, Perez Fernandez V, Wewering S, et al. Parkin loss of function contributes to RTP801 elevation and neurodegeneration in Parkinson's disease. Cell Death Dis. 2014;5:e1364 pubmed publisher
    Mutations in the PARK2 gene are associated with an autosomal recessive form of juvenile parkinsonism (AR-JP)...
  56. Lonskaya I, Desforges N, Hebron M, Moussa C. Ubiquitination increases parkin activity to promote autophagic ?-synuclein clearance. PLoS ONE. 2013;8:e83914 pubmed publisher
    ..These studies demonstrate that parkin ubiquitination affects its protein stability and E3 ligase activity, possibly leading to ?-Synuclein sequestration and subsequent clearance. ..
  57. Lo Bianco C, Schneider B, Bauer M, Sajadi A, Brice A, Iwatsubo T, et al. Lentiviral vector delivery of parkin prevents dopaminergic degeneration in an alpha-synuclein rat model of Parkinson's disease. Proc Natl Acad Sci U S A. 2004;101:17510-5 pubmed
    ..These results indicate that parkin gene therapy may represent a promising candidate treatment for PD. ..
  58. Kitao Y, Imai Y, Ozawa K, Kataoka A, Ikeda T, Soda M, et al. Pael receptor induces death of dopaminergic neurons in the substantia nigra via endoplasmic reticulum stress and dopamine toxicity, which is enhanced under condition of parkin inactivation. Hum Mol Genet. 2007;16:50-60 pubmed
    ..These data suggest a model in which ER- and dopamine-related stress are major contributors to decreased viability of dopaminergic neurons in a setting relevant to Parkinson's disease. ..
  59. Haque M, Mount M, Safarpour F, Abdel Messih E, Callaghan S, Mazerolle C, et al. Inactivation of Pink1 gene in vivo sensitizes dopamine-producing neurons to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and can be rescued by autosomal recessive Parkinson disease genes, Parkin or DJ-1. J Biol Chem. 2012;287:23162-70 pubmed publisher
  60. Walinda E, Morimoto D, Sugase K, Shirakawa M. Dual Function of Phosphoubiquitin in E3 Activation of Parkin. J Biol Chem. 2016;291:16879-91 pubmed publisher
    ..Thus, ubiquitin plays a dual role in parkin activation by competing with the inhibitory UBL domain and stabilizing the active form of parkin. ..
  61. Candeias E, Sebastião I, Cardoso S, Carvalho C, Santos M, Oliveira C, et al. Brain GLP-1/IGF-1 Signaling and Autophagy Mediate Exendin-4 Protection Against Apoptosis in Type 2 Diabetic Rats. Mol Neurobiol. 2018;55:4030-4050 pubmed publisher
    ..Altogether, this study demonstrates that peripheral Ex-4 administration may constitute a promising therapy against the chronic complications of T2D affecting the brain. ..
  62. Lee J, Nagano Y, Taylor J, Lim K, Yao T. Disease-causing mutations in parkin impair mitochondrial ubiquitination, aggregation, and HDAC6-dependent mitophagy. J Cell Biol. 2010;189:671-9 pubmed publisher
  63. Ledesma M, Galvan C, Hellias B, Dotti C, Jensen P. Astrocytic but not neuronal increased expression and redistribution of parkin during unfolded protein stress. J Neurochem. 2002;83:1431-40 pubmed
    ..The cell specific differences argue in favour of different cellular binding sites and substrates for the protein and a pathogenic role for astrocytes in Parkinson's disease caused by parkin dysfunction. ..
  64. Cortese G, Zhu M, Williams D, Heath S, Waites C. Parkin Deficiency Reduces Hippocampal Glutamatergic Neurotransmission by Impairing AMPA Receptor Endocytosis. J Neurosci. 2016;36:12243-12258 pubmed
    ..These findings demonstrate a novel role for Parkin in synaptic AMPA receptor internalization and suggest a Parkin-dependent mechanism for hippocampal dysfunction that may explain cognitive deficits associated with some forms of PD. ..
  65. Ahmed M, Zhan X, Song X, Kook S, Gurevich V, Gurevich E. Ubiquitin ligase parkin promotes Mdm2-arrestin interaction but inhibits arrestin ubiquitination. Biochemistry. 2011;50:3749-63 pubmed publisher
    ..Parkin binding to arrestins along with its effects on arrestin interaction with Mdm2 and ubiquitination is a novel function of this protein with implications for Parkinson's disease pathology. ..
  66. Sunico C, Nakamura T, Rockenstein E, Mante M, Adame A, Chan S, et al. S-Nitrosylation of parkin as a novel regulator of p53-mediated neuronal cell death in sporadic Parkinson's disease. Mol Neurodegener. 2013;8:29 pubmed publisher
    ..Taken together, our data indicate that S-nitrosylation of parkin, leading to p53-mediated neuronal cell death, contributes to the pathophysiology of sporadic PD. ..
  67. Rawal N, Corti O, Sacchetti P, Ardilla Osorio H, Sehat B, Brice A, et al. Parkin protects dopaminergic neurons from excessive Wnt/beta-catenin signaling. Biochem Biophys Res Commun. 2009;388:473-8 pubmed publisher
    ..These findings demonstrate a novel regulation of Wnt signaling by Parkin and suggest that Parkin protects DA neurons against excessive Wnt signaling and beta-catenin-induced cell death. ..