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Gene Review

park  -  parkin

Drosophila melanogaster

Synonyms: AAN12155.1, CG10523, Dmel\CG10523, Dpark, PK, ...
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Disease relevance of park

  • Parkin, an E3 ubiquitin ligase, has been found to be responsible for autosomal recessive juvenile parkinsonism characterized primarily by selective loss of dopaminergic neurons with subsequent defects in movements [1].
  • Our study implicates Parkin as a central player in the molecular pathway of Parkinson's disease (PD) and suggests that manipulating Parkin expression may provide a novel avenue of PD therapy [2].
  • Furthermore, overexpression of Parkin can mitigate alpha-Synuclein-induced neuritic pathology and suppress its toxicity [2].
  • Drosophila parkin null mutants exhibit reduced lifespan, locomotor defects, and male sterility [3].
  • Neurodegenerative disease: pink, parkin and the brain [4].

High impact information on park

  • Parkin negatively regulates JNK pathway in the dopaminergic neurons of Drosophila [1].
  • Here, we characterized Drosophila parkin loss-of-function mutants, which exhibit shrinkage of dopaminergic neurons with decreased tyrosine hydroxylase level and impaired locomotion [1].
  • These results suggest that loss of Parkin function up-regulates the JNK signaling pathway, which may contribute to the vulnerability of dopaminergic neurons in Drosophila parkin mutants and perhaps autosomal recessive juvenile parkinsonism patients [1].
  • The behavioral defect of parkin mutant flies was partially restored by administering L-DOPA, and the dopamine level in the brains of parkin mutant flies was highly decreased [1].
  • Furthermore, overexpression of GstS1 in DA neurons suppresses neurodegeneration in parkin mutants [5].

Chemical compound and disease context of park


Biological context of park

  • These results indicate that the tissue-specific phenotypes observed in Drosophila parkin mutants result from mitochondrial dysfunction and raise the possibility that similar mitochondrial impairment triggers the selective cell loss observed in AR-JP [3].
  • Drosophila parkin mutants have decreased mass and cell size and increased sensitivity to oxygen radical stress [6].
  • Furthermore, loss of parkin results in progressive degeneration of most indirect flight muscle (IFM) groups soon after eclosion, accompanied by apoptosis [6].
  • Using the yeast two-hybrid screen, we isolated a RING finger protein that interacted with the N terminus of parkin in a Drosophila cDNA library [7].
  • The amino acid sequence of D. melanogaster Parkin exhibits 42%, 43% and 43% identity to that of human, mouse and rat, respectively, representing a 54 kDa protein band via western blot analysis [8].

Anatomical context of park

  • Mitochondrial pathology is the earliest manifestation of muscle degeneration and a prominent characteristic of individualizing spermatids in parkin mutants [3].
  • However, parkin mutants have normal neuromuscular junction recordings during the third larval instar stage, suggesting that larval musculature is intact and that parkin is required only in pupal and adult muscle. parkin flies do not show an age-dependent dopaminergic neuron loss in the brain, even after aging adults for 3 weeks [6].
  • From immunostainings of the embryo, D. melanogaster parkin was expressed slightly higher in the central nervous system (brain and nerve cord) during the late embryonic stage [8].
  • While in some instances Parkin-containing neurons tended to be grouped into clusters, the majority of these labeled nerve cells were widely scattered throughout the neuraxis [9].
  • Further investigation of parkin expression in skeletal muscle is warranted [10].

Associations of park with chemical compounds

  • Using an antibody against a peptide corresponding to sequence number 305-323 of the human parkin protein it was demonstrated that parkin was expressed in skeletal muscle of these patients and that its distribution was similar to that in normal muscles [10].

Regulatory relationships of park


Analytical, diagnostic and therapeutic context of park

  • Western blotting and immunocytochemistry showed a much stronger expression level for HA-parkin residues 77-465 (without ULD) than HA-parkin full-length (with ULD) [11].
  • The expression pattern of D. melanogaster parkin varies during the developmental stages, with the highest expression in the adult stage as measured by competitive RT-PCR [8].


  1. Parkin negatively regulates JNK pathway in the dopaminergic neurons of Drosophila. Cha, G.H., Kim, S., Park, J., Lee, E., Kim, M., Lee, S.B., Kim, J.M., Chung, J., Cho, K.S. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  2. Parkin suppresses dopaminergic neuron-selective neurotoxicity induced by Pael-R in Drosophila. Yang, Y., Nishimura, I., Imai, Y., Takahashi, R., Lu, B. Neuron (2003) [Pubmed]
  3. Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants. Greene, J.C., Whitworth, A.J., Kuo, I., Andrews, L.A., Feany, M.B., Pallanck, L.J. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  4. Neurodegenerative disease: pink, parkin and the brain. Pallanck, L., Greenamyre, J.T. Nature (2006) [Pubmed]
  5. Increased glutathione S-transferase activity rescues dopaminergic neuron loss in a Drosophila model of Parkinson's disease. Whitworth, A.J., Theodore, D.A., Greene, J.C., Benes, H., Wes, P.D., Pallanck, L.J. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  6. Drosophila parkin mutants have decreased mass and cell size and increased sensitivity to oxygen radical stress. Pesah, Y., Pham, T., Burgess, H., Middlebrooks, B., Verstreken, P., Zhou, Y., Harding, M., Bellen, H., Mardon, G. Development (2004) [Pubmed]
  7. RING finger ubiquitin-protein isopeptide ligase Nrdp1/FLRF regulates parkin stability and activity. Zhong, L., Tan, Y., Zhou, A., Yu, Q., Zhou, J. J. Biol. Chem. (2005) [Pubmed]
  8. Genomic organization and expression of parkin in Drosophila melanogaster. Bae, Y.J., Park, K.S., Kang, S.J. Exp. Mol. Med. (2003) [Pubmed]
  9. Immunodetection of Parkin protein in vertebrate and invertebrate brains: a comparative study using specific antibodies. Horowitz, J.M., Vernace, V.A., Myers, J., Stachowiak, M.K., Hanlon, D.W., Fraley, G.S., Torres, G. J. Chem. Neuroanat. (2001) [Pubmed]
  10. Parkin expression in muscle from three patients with autosomal recessive Parkinson's disease carrying parkin mutation. Serdaroglu, P., Hanagasi, H., Tasli, H., Emre, M. Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology / edited by the Gaetano Conte Academy for the study of striated muscle diseases. (2005) [Pubmed]
  11. The cellular protein level of parkin is regulated by its ubiquitin-like domain. Finney, N., Walther, F., Mantel, P.Y., Stauffer, D., Rovelli, G., Dev, K.K. J. Biol. Chem. (2003) [Pubmed]
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