Parkinson's disease (WP3638)

Mus musculus

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Most people with Parkinson's disease have idiopathic Parkinson's disease (having no specific known cause). A small proportion of cases, however, can be attributed to known genetic factors. Mutations in specific genes have been conclusively shown to cause PD. These genes code for alpha-synuclein (SNCA), parkin (PRKN), leucine-rich repeat kinase 2 (LRRK2 or dardarin), PTEN-induced putative kinase 1 (PINK1), DJ-1 and ATP13A2.[4][22] In most cases, people with these mutations will develop PD. With the exception of LRRK2, however, they account for only a small minority of cases of PD.[4] The most extensively studied PD-related genes are SNCA and LRRK2. Mutations in genes including SNCA, LRRK2 and glucocerebrosidase (GBA) have been found to be risk factors for sporadic PD. The role of the SNCA gene is important in PD because the alpha-synuclein protein is the main component of Lewy bodies.[22] Missense mutations of the gene (in which a single nucleotide is changed), and duplications and triplications of the locus containing it have been found in different groups with familial PD. Mutations in LRRK2 are the most common known cause of familial and sporadic PD, accounting for approximately 5% of individuals with a family history of the disease and 3% of sporadic cases. This is an updated copy of the human parkinson disease pathway (WP2371). Sources: [http://en.wikipedia.org/wiki/Parkinson's_disease wikipedia], [https://www.qiagen.com/geneglobe/pathwayview.aspx?pathwayID=345 Quigen], and [http://www.genome.jp/kegg/pathway/hsa/hsa05012.html KEGG].

Authors

Friederike Ehrhart , Mick Eikelhof , Eric Weitz , Egon Willighagen , and Alex Pico

Activity

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Cited In

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Organisms

Mus musculus

Communities

Diseases ExRNA

Annotations

Disease Ontology

Parkinson's disease Lewy body dementia

Pathway Ontology

disease pathway neurodegenerative pathway Parkinson's disease pathway

Cell Type Ontology

neuron

Participants

Label Type Compact URI Comment
ROS Metabolite chebi:26523
L-Tyrosine Metabolite kegg.compound:C00082
L-DOPA Metabolite kegg.compound:C00355
Dopamine Metabolite kegg.compound:C03758
Dopamine Metabolite kegg.compound:C03758
Eprs GeneProduct ensembl:ENSMUSG00000026615
Ddc GeneProduct ensembl:ENSMUSG00000020182
Slc6a3 GeneProduct ensembl:ENSMUSG00000021609
Uchl1 GeneProduct ensembl:ENSMUSG00000029223
Park2 GeneProduct ensembl:ENSMUSG00000023826
Snca GeneProduct ensembl:ENSMUSG00000025889
Th GeneProduct ensembl:ENSMUSG00000000214
Lrrk2 GeneProduct ensembl:ENSMUSG00000036273
Pink1 GeneProduct ensembl:ENSMUSG00000028756
Park7 GeneProduct ensembl:ENSMUSG00000028964
Htra2 GeneProduct ensembl:ENSMUSG00000068329
Cycs GeneProduct ensembl:ENSMUSG00000063694
Gpr37 GeneProduct ensembl:ENSMUSG00000039904
Sept5 GeneProduct ensembl:ENSMUSG00000072214
Sncaip GeneProduct ensembl:ENSMUSG00000024534
Ubb GeneProduct ensembl:ENSMUSG00000019505
Uba1 GeneProduct ensembl:ENSMUSG00000001924
Uba7 GeneProduct ensembl:ENSMUSG00000032596
Ube2l3 GeneProduct ensembl:ENSMUSG00000038965
Ube2l6 GeneProduct ensembl:ENSMUSG00000027078
Ube2j2 GeneProduct ensembl:ENSMUSG00000023286
Ube2g1 GeneProduct ensembl:ENSMUSG00000020794
Ube2g2 GeneProduct ensembl:ENSMUSG00000009293
Ube2j1 GeneProduct ensembl:ENSMUSG00000028277
Atxn2 GeneProduct ensembl:ENSMUSG00000042605
Syt11 GeneProduct ensembl:ENSMUSG00000068923
Ccne1 GeneProduct ensembl:ENSMUSG00000002068
Ccne2 GeneProduct ensembl:ENSMUSG00000028212
Snca GeneProduct ensembl:ENSMUSG00000025889
Sncaip GeneProduct ensembl:ENSMUSG00000024534
Mapk12 GeneProduct ensembl:ENSMUSG00000022610
Mapk11 GeneProduct ensembl:ENSMUSG00000053137
Mapk14 GeneProduct ensembl:ENSMUSG00000053436
Mapk13 GeneProduct ensembl:ENSMUSG00000004864
Casp6 GeneProduct ensembl:ENSMUSG00000027997
Casp9 GeneProduct ensembl:ENSMUSG00000028914
Casp2 GeneProduct ensembl:ENSMUSG00000029863
Cycs GeneProduct ensembl:ENSMUSG00000063694
Casp7 GeneProduct ensembl:ENSMUSG00000025076
Casp3 GeneProduct ensembl:ENSMUSG00000031628
Apaf1 GeneProduct ensembl:ENSMUSG00000019979

References

  1. Parkin is a component of an SCF-like ubiquitin ligase complex and protects postmitotic neurons from kainate excitotoxicity. Staropoli JF, McDermott C, Martinat C, Schulman B, Demireva E, Abeliovich A. Neuron. 2003 Mar 6;37(5):735–49. PubMed Europe PMC Scholia
  2. Parkin binds to alpha/beta tubulin and increases their ubiquitination and degradation. Ren Y, Zhao J, Feng J. J Neurosci. 2003 Apr 15;23(8):3316–24. PubMed Europe PMC Scholia
  3. Targeting programmed cell death in neurodegenerative diseases. Vila M, Przedborski S. Nat Rev Neurosci. 2003 May;4(5):365–75. PubMed Europe PMC Scholia
  4. The p38 subunit of the aminoacyl-tRNA synthetase complex is a Parkin substrate: linking protein biosynthesis and neurodegeneration. Corti O, Hampe C, Koutnikova H, Darios F, Jacquier S, Prigent A, et al. Hum Mol Genet. 2003 Jun 15;12(12):1427–37. PubMed Europe PMC Scholia
  5. Does alpha-synuclein modulate dopaminergic synaptic content and tone at the synapse? Sidhu A, Wersinger C, Vernier P. FASEB J. 2004 Apr;18(6):637–47. PubMed Europe PMC Scholia
  6. How does parkin ligate ubiquitin to Parkinson’s disease? Kahle PJ, Haass C. EMBO Rep. 2004 Jul;5(7):681–5. PubMed Europe PMC Scholia
  7. Causes of Parkinson’s disease: genetics of DJ-1. Abou-Sleiman PM, Healy DG, Wood NW. Cell Tissue Res. 2004 Oct;318(1):185–8. PubMed Europe PMC Scholia
  8. What does PINK1 mean for Parkinson diseases? Singleton A. Neurology. 2004 Oct 26;63(8):1350–1. PubMed Europe PMC Scholia
  9. The gene products for familial Parkinson’s disease provide us hints to elucidate the mechanisms of nigral degeneration. Hattori N. Rinsho Shinkeigaku. 2004 Nov;44(11):821–3. PubMed Europe PMC Scholia
  10. Common anti-apoptotic roles of parkin and alpha-synuclein in human dopaminergic cells. Machida Y, Chiba T, Takayanagi A, Tanaka Y, Asanuma M, Ogawa N, et al. Biochem Biophys Res Commun. 2005 Jun 24;332(1):233–40. PubMed Europe PMC Scholia
  11. The biochemistry of Parkinson’s disease. Cookson MR. Annu Rev Biochem. 2005;74:29–52. PubMed Europe PMC Scholia
  12. Molecular pathophysiology of Parkinson’s disease. Moore DJ, West AB, Dawson VL, Dawson TM. Annu Rev Neurosci. 2005;28:57–87. PubMed Europe PMC Scholia
  13. Expanding insights of mitochondrial dysfunction in Parkinson’s disease. Abou-Sleiman PM, Muqit MMK, Wood NW. Nat Rev Neurosci. 2006 Mar;7(3):207–19. PubMed Europe PMC Scholia
  14. Parkinson’s disease. Thomas B, Beal MF. Hum Mol Genet. 2007 Oct 15;16 Spec No. 2:R183-94. PubMed Europe PMC Scholia
  15. Progress in the pathogenesis and genetics of Parkinson’s disease. Mizuno Y, Hattori N, Kubo SI, Sato S, Nishioka K, Hatano T, et al. Philos Trans R Soc Lond B Biol Sci. 2008 Jun 27;363(1500):2215–27. PubMed Europe PMC Scholia
  16. Mitochondrial alterations in Parkinson’s disease: new clues. Vila M, Ramonet D, Perier C. J Neurochem. 2008 Oct;107(2):317–28. PubMed Europe PMC Scholia
  17. MicroRNA target prediction by expression analysis of host genes. Gennarino VA, Sardiello M, Avellino R, Meola N, Maselli V, Anand S, et al. Genome Res. 2009 Mar;19(3):481–90. PubMed Europe PMC Scholia
  18. The miR-34 family in cancer and apoptosis. Hermeking H. Cell Death Differ. 2010 Feb;17(2):193–9. PubMed Europe PMC Scholia
  19. Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Kota J, Chivukula RR, O’Donnell KA, Wentzel EA, Montgomery CL, Hwang HW, et al. Cell. 2009 Jun 12;137(6):1005–17. PubMed Europe PMC Scholia
  20. Induction of microRNAs, mir-155, mir-222, mir-424 and mir-503, promotes monocytic differentiation through combinatorial regulation. Forrest ARR, Kanamori-Katayama M, Tomaru Y, Lassmann T, Ninomiya N, Takahashi Y, et al. Leukemia. 2010 Feb;24(2):460–6. PubMed Europe PMC Scholia
  21. miR-375 inhibits differentiation of neurites by lowering HuD levels. Abdelmohsen K, Hutchison ER, Lee EK, Kuwano Y, Kim MM, Masuda K, et al. Mol Cell Biol. 2010 Sep;30(17):4197–210. PubMed Europe PMC Scholia
  22. MicroRNA-195 inhibits the proliferation of human glioma cells by directly targeting cyclin D1 and cyclin E1. Hui W, Yuntao L, Lun L, WenSheng L, ChaoFeng L, HaiYong H, et al. PLoS One. 2013;8(1):e54932. PubMed Europe PMC Scholia
  23. Profiles of extracellular miRNA in cerebrospinal fluid and serum from patients with Alzheimer’s and Parkinson’s diseases correlate with disease status and features of pathology. Burgos K, Malenica I, Metpally R, Courtright A, Rakela B, Beach T, et al. PLoS One. 2014 May 5;9(5):e94839. PubMed Europe PMC Scholia