Parkinson's disease pathway (WP2371)

Homo sapiens

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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. Sources: [http://en.wikipedia.org/wiki/Parkinson's_disease wikipedia], [https://www.qiagen.com/geneglobe/pathwayview.aspx?pathwayID=345 Qiagen], and [http://www.genome.jp/kegg/pathway/hsa/hsa05012.html KEGG]. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP2371 CPTAC Assay Portal]

Authors

Alex Pico , Egon Willighagen , Kristina Hanspers , Friederike Ehrhart , Martina Summer-Kutmon , and Eric Weitz

Activity

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Organisms

Homo sapiens

Communities

Diseases ExRNA Rare Diseases

Annotations

Pathway Ontology

disease pathway Parkinson's disease pathway neurodegenerative pathway

Disease Ontology

Lewy body dementia neurodegenerative disease Parkinson's disease

Cell Type Ontology

dopaminergic neuron

Participants
Query Drugst.One

Label Type Compact URI Comment
ROS Metabolite chebi:29191
L-Tyrosine Metabolite kegg.compound:C00082
L-DOPA Metabolite kegg.compound:C00355
Dopamine Metabolite kegg.compound:C03758
Dopamine Metabolite kegg.compound:C03758
EPRS GeneProduct ncbigene:2058
DDC GeneProduct ncbigene:1644
DAT GeneProduct ncbigene:6531
UCHL1 GeneProduct ncbigene:7345
Parkin GeneProduct ncbigene:5071
SNCA GeneProduct ncbigene:6622
TH GeneProduct ncbigene:7054
LRRK2 GeneProduct ncbigene:120892
PINK1 GeneProduct ncbigene:65018
DJ1 GeneProduct ncbigene:11315
HTRA2 GeneProduct ncbigene:27429
CYCS GeneProduct ncbigene:54205
GPR37 GeneProduct ncbigene:2861
SEPTIN5 GeneProduct ncbigene:5413
SNCAIP GeneProduct ncbigene:9627
UBB GeneProduct ncbigene:7314
UBA1 GeneProduct ncbigene:7317
UBA7 GeneProduct ncbigene:7318
UBE2L3 GeneProduct ncbigene:7332
UBE2L6 GeneProduct ncbigene:9246
UBE2J2 GeneProduct ncbigene:118424
UBE2G1 GeneProduct ncbigene:7326
UBE2G2 GeneProduct ncbigene:7327
UBE2J1 GeneProduct ncbigene:51465
ATXN2 GeneProduct ncbigene:6311
SYT11 GeneProduct ncbigene:23208
CCNE1 GeneProduct ncbigene:898
CCNE2 GeneProduct ncbigene:9134
SNCA GeneProduct ncbigene:6622
SNCAIP GeneProduct ncbigene:9627
MAPK12 GeneProduct ncbigene:6300
MAPK11 GeneProduct ncbigene:5600
MAPK14 GeneProduct ncbigene:1432
MAPK13 GeneProduct ncbigene:5603
CASP6 GeneProduct ncbigene:839
CASP9 GeneProduct ncbigene:842
CASP2 GeneProduct ncbigene:835
CYCS GeneProduct ncbigene:54205
CASP7 GeneProduct ncbigene:840
CASP3 GeneProduct ncbigene:836
APAF1 GeneProduct ncbigene:317

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. Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP. Hafner M, Landthaler M, Burger L, Khorshid M, Hausser J, Berninger P, et al. Cell. 2010 Apr 2;141(1):129–41. PubMed Europe PMC Scholia
  22. 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
  23. 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
  24. 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