Parkinsons Disease Pathway (Homo sapiens)

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Description

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: wikipedia, Quigen, and KEGG.

Ontology Tags

 

Bibliography

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  1. Ren Y, Zhao J, Feng J; ''Parkin binds to alpha/beta tubulin and increases their ubiquitination and degradation.''; J Neurosci, 2003 PubMed
  2. Singleton A; ''What does PINK1 mean for Parkinson diseases?''; Neurology, 2004 PubMed
  3. Mizuno Y, Hattori N, Kubo S, Sato S, Nishioka K, Hatano T, Tomiyama H, Funayama M, Machida Y, Mochizuki H; ''Progress in the pathogenesis and genetics of Parkinson's disease.''; Philos Trans R Soc Lond B Biol Sci, 2008 PubMed
  4. Machida Y, Chiba T, Takayanagi A, Tanaka Y, Asanuma M, Ogawa N, Koyama A, Iwatsubo T, Ito S, Jansen PH, Shimizu N, Tanaka K, Mizuno Y, Hattori N; ''Common anti-apoptotic roles of parkin and alpha-synuclein in human dopaminergic cells.''; Biochem Biophys Res Commun, 2005 PubMed
  5. Cookson MR; ''The biochemistry of Parkinson's disease.''; Annu Rev Biochem, 2005 PubMed
  6. Kahle PJ, Haass C; ''How does parkin ligate ubiquitin to Parkinson's disease?''; EMBO Rep, 2004 PubMed
  7. Burgos K, Malenica I, Metpally R, Courtright A, Rakela B, Beach T, Shill H, Adler C, Sabbagh M, Villa S, Tembe W, Craig D, Van Keuren-Jensen K; ''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.''; PLoS One, 2014 PubMed
  8. Staropoli JF, 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 PubMed
  9. Corti O, Hampe C, Koutnikova H, Darios F, Jacquier S, Prigent A, Robinson JC, Pradier L, Ruberg M, Mirande M, Hirsch E, Rooney T, Fournier A, Brice A; ''The p38 subunit of the aminoacyl-tRNA synthetase complex is a Parkin substrate: linking protein biosynthesis and neurodegeneration.''; Hum Mol Genet, 2003 PubMed
  10. Thomas B, Beal MF; ''Parkinson's disease.''; Hum Mol Genet, 2007 PubMed
  11. Vila M, Przedborski S; ''Targeting programmed cell death in neurodegenerative diseases.''; Nat Rev Neurosci, 2003 PubMed
  12. Abou-Sleiman PM, Muqit MM, Wood NW; ''Expanding insights of mitochondrial dysfunction in Parkinson's disease.''; Nat Rev Neurosci, 2006 PubMed
  13. Sidhu A, Wersinger C, Vernier P; ''Does alpha-synuclein modulate dopaminergic synaptic content and tone at the synapse?''; FASEB J, 2004 PubMed
  14. Moore DJ, West AB, Dawson VL, Dawson TM; ''Molecular pathophysiology of Parkinson's disease.''; Annu Rev Neurosci, 2005 PubMed
  15. Abou-Sleiman PM, Healy DG, Wood NW; ''Causes of Parkinson's disease: genetics of DJ-1.''; Cell Tissue Res, 2004 PubMed
  16. Vila M, Ramonet D, Perier C; ''Mitochondrial alterations in Parkinson's disease: new clues.''; J Neurochem, 2008 PubMed
  17. Hattori N; ''[The gene products for familial Parkinson's disease provide us hints to elucidate the mechanisms of nigral degeneration].''; Rinsho Shinkeigaku, 2004 PubMed
  18. Hermeking H; ''The miR-34 family in cancer and apoptosis.''; Cell Death Differ, 2010 PubMed
  19. Kota J, Chivukula RR, O'Donnell KA, Wentzel EA, Montgomery CL, Hwang HW, Chang TC, Vivekanandan P, Torbenson M, Clark KR, Mendell JR, Mendell JT; ''Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model.''; Cell, 2009 PubMed
  20. Forrest AR, Kanamori-Katayama M, Tomaru Y, Lassmann T, Ninomiya N, Takahashi Y, de Hoon MJ, Kubosaki A, Kaiho A, Suzuki M, Yasuda J, Kawai J, Hayashizaki Y, Hume DA, Suzuki H; ''Induction of microRNAs, mir-155, mir-222, mir-424 and mir-503, promotes monocytic differentiation through combinatorial regulation.''; Leukemia, 2010 PubMed
  21. Hui W, Yuntao L, Lun L, WenSheng L, ChaoFeng L, HaiYong H, Yueyang B; ''MicroRNA-195 inhibits the proliferation of human glioma cells by directly targeting cyclin D1 and cyclin E1.''; PLoS One, 2013 PubMed
  22. Hafner M, Landthaler M, Burger L, Khorshid M, Hausser J, Berninger P, Rothballer A, Ascano M Jr, Jungkamp AC, Munschauer M, Ulrich A, Wardle GS, Dewell S, Zavolan M, Tuschl T; ''Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP.''; Cell, 2010 PubMed
  23. Abdelmohsen K, Hutchison ER, Lee EK, Kuwano Y, Kim MM, Masuda K, Srikantan S, Subaran SS, Marasa BS, Mattson MP, Gorospe M; ''miR-375 inhibits differentiation of neurites by lowering HuD levels.''; Mol Cell Biol, 2010 PubMed
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History

View all...
CompareRevisionActionTimeUserComment
79766view02:58, 11 April 2015AlexanderPicoAdded miRNA interactions and refs
79311view21:45, 20 March 2015Khansperscleanup
79310view21:43, 20 March 2015Khanspersredraw bounding box for miRNAs
79309view21:39, 20 March 2015Khanspersmoved new rna nodes
79308view21:38, 20 March 2015Khanspersadding new RNA nodes
79307view21:35, 20 March 2015Khansperstesting ungrouping
79306view21:34, 20 March 2015Khanspersmoved miRNA box
79304view19:18, 20 March 2015AlexanderPicoupdated type to Rna
79301view19:03, 20 March 2015AlexanderPicoupdated miRNA label
78942view22:48, 16 February 2015KhanspersAdded lit ref as label
78940view22:37, 16 February 2015Khanspersmoved miRNA box
78939view22:34, 16 February 2015Khanspersmove miRNA box
78938view22:30, 16 February 2015KhanspersAdded miRNAs from Burgos et al
78809view09:46, 31 January 2015EgonwUpdated an DataNode and Interaction with pure graphical elements.
71267view21:55, 16 October 2013MaintBotAutomated update of data sources
69744view09:16, 11 July 2013EgonwRemoved a space in the identifier.
68997view17:44, 8 July 2013MaintBotUpdated to 2013 gpml schema
54138view00:08, 22 November 2012AlexanderPicoAdded literature references
54137view23:54, 21 November 2012AlexanderPiconew lit refs
54136view23:52, 21 November 2012AlexanderPico
54135view23:48, 21 November 2012AlexanderPico
54046view01:54, 19 November 2012AlexanderPicoOntology Term : 'neurodegenerative disease pathway' added !
54045view01:54, 19 November 2012AlexanderPicoOntology Term : 'neurodegenerative disease' added !
54044view01:53, 19 November 2012AlexanderPicoOntology Term : 'Lewy body dementia' added !
54043view01:53, 19 November 2012AlexanderPicoOntology Term : 'Parkinson's disease' added !
54042view01:53, 19 November 2012AlexanderPicoOntology Term : 'Parkinson disease pathway' added !
54041view01:52, 19 November 2012AlexanderPicoModified categories
54040view01:50, 19 November 2012AlexanderPicoModified description
54039view01:50, 19 November 2012AlexanderPicoModified description
54038view01:41, 19 November 2012AlexanderPicoNew pathway

External references

View all...
NameTypeDatabase referenceComment
MIR1224Rna100187716 (Entrez Gene)
ROSMetabolite29191 (ChEBI)
MIR19ARna406979 (Entrez Gene)
Apoptosis PathwayPathwayWP254 (WikiPathways)
DDCGeneProduct1644 (Entrez Gene)
EPRSGeneProduct2058 (Entrez Gene)
MIRLET7GRna406890 (Entrez Gene)
DATGeneProduct6531 (Entrez Gene)
MIR34CGeneProduct407042 (Entrez Gene)
UCHL1GeneProduct7345 (Entrez Gene)
APAF1GeneProduct317 (Entrez Gene)
ParkinGeneProduct5071 (Entrez Gene)
MIR127Rna406914 (Entrez Gene)
SNCAGeneProduct6622 (Entrez Gene)
MIR431Rna574038 (Entrez Gene)
THGeneProduct7054 (Entrez Gene)
MIR1294Rna100302181 (Entrez Gene)
L-TyrosineMetaboliteC00082 (KEGG Compound)
MIR195GeneProduct406971 (Entrez Gene)
L-DOPAMetaboliteC00355 (KEGG Compound)
CASP7GeneProduct840 (Entrez Gene)
DopamineMetaboliteC03758 (KEGG Compound)
WNT SignalingPathwayWP399 (WikiPathways)
LRRK2GeneProduct120892 (Entrez Gene)
MIR19B2Rna406981 (Entrez Gene)
PINK1GeneProduct65018 (Entrez Gene)
MIR128-2Rna406916 (Entrez Gene)
DJ1GeneProduct11315 (Entrez Gene)
MIR370Rna442915 (Entrez Gene)
HTRA2GeneProduct27429 (Entrez Gene)
MIR212Rna406994 (Entrez Gene)
CYCSGeneProduct54205 (Entrez Gene)
MIR338Rna442906 (Entrez Gene)
GPR37GeneProduct2861 (Entrez Gene)
MIR30ARna407029 (Entrez Gene)
SEPT5GeneProduct5413 (Entrez Gene)
MIR26A2GeneProduct407016 (Entrez Gene)
SNCAIPGeneProduct9627 (Entrez Gene)
MIR18AGeneProduct406953 (Entrez Gene)
UBBGeneProduct7314 (Entrez Gene)
CASP2GeneProduct835 (Entrez Gene)
UBA1GeneProduct7317 (Entrez Gene)
CASP3GeneProduct836 (Entrez Gene)
UBA7GeneProduct7318 (Entrez Gene)
MAPK SignalingPathwayWP382 (WikiPathways)
UBE2L3GeneProduct7332 (Entrez Gene)
MIR132Rna406921 (Entrez Gene)
UBE2L6GeneProduct9246 (Entrez Gene)
MIR19B1Rna406980 (Entrez Gene)
UBE2J2GeneProduct118424 (Entrez Gene)
MIR485Rna574436 (Entrez Gene)
UBE2G1GeneProduct7326 (Entrez Gene)
MIR128-1Rna406915 (Entrez Gene)
UBE2G2GeneProduct7327 (Entrez Gene)
MIR409Rna574413 (Entrez Gene)
UBE2J1GeneProduct51465 (Entrez Gene)
MIR433Rna574034 (Entrez Gene)
ATXN2GeneProduct6311 (Entrez Gene)
MIR873Rna100126316 (Entrez Gene)
SYT11GeneProduct23208 (Entrez Gene)
MIR136Rna406927 (Entrez Gene)
CCNE1GeneProduct898 (Entrez Gene)
MIR10ARna406902 (Entrez Gene)
CCNE2GeneProduct9134 (Entrez Gene)
MIR4448Rna100616127 (Entrez Gene)
MAPK12GeneProduct6300 (Entrez Gene)
MIR16-2Rna406951 (Entrez Gene)
MAPK11GeneProduct5600 (Entrez Gene)
MIR30ERna407034 (Entrez Gene)
MAPK14GeneProduct1432 (Entrez Gene)
MIR503GeneProduct574506 (Entrez Gene)
MAPK13GeneProduct5603 (Entrez Gene)
MIR26A1GeneProduct407015 (Entrez Gene)
Oxidative PhosphorylationPathwayWP111 (WikiPathways)
MIR34BGeneProduct407041 (Entrez Gene)
CASP6GeneProduct839 (Entrez Gene)
MIR26BGeneProduct407017 (Entrez Gene)
CASP9GeneProduct842 (Entrez Gene)
MIR375GeneProduct494324 (Entrez Gene)
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