Parkinson's disease pathway (Homo sapiens)

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2, 8, 12-1415ProteinO-glycosylationUbiquitin pathway componentsOxidative StressLewy BodyXROSEPRSDDCApoptosis PathwayDATUCHL1ParkinSNCATH6L-TyrosineL-DOPADopamineDopamineLRRK2PINK111DJ1HTRA217CYCSGPR37SEPT5SNCAIPUBBUBA1UBA7UBE2L3UBE2L6UBE2J2UBE2G1UBE2G2UBE2J1Targets for Ub degradationATXN21, 3, 7, 16SYT11CCNE1CCNE2SNCASNCAIPMAPK12MAPK11MAPK14MAPK13XXAggregationCell DeathDopamine oxidationUb Proteosome SystemDysfunctionToxicityDopaminergic NeuronMitochondrialDysfunction4, 15OxidativePhosphorylationApoptosis PathwayCell Death9CASP6CASP9CASP2CYCSCASP7CASP3APAF1XMAPK SignalingWNT SignalingXParkinson's disease genes:pathogenic mutationsBlock of normal functionfor mutated genesIndirect actionMIR132MIR19AMIR19B1MIR19B2MIR485MIR127MIR128-1MIR128-2MIR409MIRLET7GMIR433MIR370MIR873MIR431MIR136MIR212MIR10AMIR1224MIR4448miRNA differentially expressed in PD(measured in cerebrospinal fluid)MIR338MIR16-2MIR1294MIR30EMIR30AmiRNA differentially expressed in PD(measured in blood serum)10Based on Table 1 from Burgos et al, PLoS ONE 2014 May.


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.

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Bibliography

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  1. Cookson MR; ''The biochemistry of Parkinson's disease.''; Annu Rev Biochem, 2005 PubMed Europe PMC Scholia
  2. Abou-Sleiman PM, Healy DG, Wood NW; ''Causes of Parkinson's disease: genetics of DJ-1.''; Cell Tissue Res, 2004 PubMed Europe PMC Scholia
  3. Moore DJ, West AB, Dawson VL, Dawson TM; ''Molecular pathophysiology of Parkinson's disease.''; Annu Rev Neurosci, 2005 PubMed Europe PMC Scholia
  4. 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 Europe PMC Scholia
  5. Ren Y, Zhao J, Feng J; ''Parkin binds to alpha/beta tubulin and increases their ubiquitination and degradation.''; J Neurosci, 2003 PubMed Europe PMC Scholia
  6. 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 Europe PMC Scholia
  7. Thomas B, Beal MF; ''Parkinson's disease.''; Hum Mol Genet, 2007 PubMed Europe PMC Scholia
  8. Abou-Sleiman PM, Muqit MM, Wood NW; ''Expanding insights of mitochondrial dysfunction in Parkinson's disease.''; Nat Rev Neurosci, 2006 PubMed Europe PMC Scholia
  9. 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 Europe PMC Scholia
  10. 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 Europe PMC Scholia
  11. 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 Europe PMC Scholia
  12. Hermeking H; ''The miR-34 family in cancer and apoptosis.''; Cell Death Differ, 2010 PubMed Europe PMC Scholia
  13. Kahle PJ, Haass C; ''How does parkin ligate ubiquitin to Parkinson's disease?''; EMBO Rep, 2004 PubMed Europe PMC Scholia
  14. 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 Europe PMC Scholia
  15. Vila M, Przedborski S; ''Targeting programmed cell death in neurodegenerative diseases.''; Nat Rev Neurosci, 2003 PubMed Europe PMC Scholia
  16. Gennarino VA, Sardiello M, Avellino R, Meola N, Maselli V, Anand S, Cutillo L, Ballabio A, Banfi S; ''MicroRNA target prediction by expression analysis of host genes.''; Genome Res, 2009 PubMed Europe PMC Scholia
  17. 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 Europe PMC Scholia
  18. Vila M, Ramonet D, Perier C; ''Mitochondrial alterations in Parkinson's disease: new clues.''; J Neurochem, 2008 PubMed Europe PMC Scholia
  19. 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 Europe PMC Scholia
  20. Hattori N; ''[The gene products for familial Parkinson's disease provide us hints to elucidate the mechanisms of nigral degeneration].''; Rinsho Shinkeigaku, 2004 PubMed Europe PMC Scholia
  21. Sidhu A, Wersinger C, Vernier P; ''Does alpha-synuclein modulate dopaminergic synaptic content and tone at the synapse?''; FASEB J, 2004 PubMed Europe PMC Scholia
  22. Singleton A; ''What does PINK1 mean for Parkinson diseases?''; Neurology, 2004 PubMed Europe PMC Scholia
  23. 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 Europe PMC Scholia
  24. 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 Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
128291view02:46, 30 January 2024EweitzOntology Term : 'dopaminergic neuron' added !
128290view02:43, 30 January 2024EweitzStandardize case
126375view17:53, 25 April 2023EgonwLicense is CCZero
119919view09:07, 17 September 2021FehrhartUpdated SEPT5 to SEPTIN5 label
116459view10:03, 7 May 2021EweitzModified title
115348view10:31, 15 February 2021EgonwMade five more pathways clickable
108090view11:56, 28 November 2019FehrhartOntology Term : 'disease pathway' added !
107127view14:20, 17 September 2019MaintBotChEBI identifier normalization
106547view00:11, 6 September 2019KhanspersModified description
105779view19:42, 15 August 2019KhanspersModified description
102996view14:40, 31 January 2019Mkutmonupdated outdated ensembl identifier
87374view09:56, 22 July 2016MaintBotadded missing graphids
85262view11:18, 4 May 2016FehrhartApplied actual nomenclature to miRNA, set biological type to RNA
85112view22:26, 15 April 2016AlexanderPicotypo fixe
85111view22:26, 15 April 2016AlexanderPicoAdjusting labels
84649view22:16, 10 March 2016KhanspersQuick edit to datanode annotation or property
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

DataNodes

View all...
NameTypeDatabase referenceComment
APAF1GeneProduct317 (Entrez Gene)
ATXN2GeneProduct6311 (Entrez Gene)
Apoptosis PathwayPathwayWP254 (WikiPathways)
CASP2GeneProduct835 (Entrez Gene)
CASP3GeneProduct836 (Entrez Gene)
CASP6GeneProduct839 (Entrez Gene)
CASP7GeneProduct840 (Entrez Gene)
CASP9GeneProduct842 (Entrez Gene)
CCNE1GeneProduct898 (Entrez Gene)
CCNE2GeneProduct9134 (Entrez Gene)
CYCSGeneProduct54205 (Entrez Gene)
DATGeneProduct6531 (Entrez Gene)
DDCGeneProduct1644 (Entrez Gene)
DJ1GeneProduct11315 (Entrez Gene)
DopamineMetaboliteC03758 (KEGG Compound)
EPRSGeneProduct2058 (Entrez Gene)
GPR37GeneProduct2861 (Entrez Gene)
HTRA2GeneProduct27429 (Entrez Gene)
L-DOPAMetaboliteC00355 (KEGG Compound)
L-TyrosineMetaboliteC00082 (KEGG Compound)
LRRK2GeneProduct120892 (Entrez Gene)
MAPK SignalingPathwayWP382 (WikiPathways)
MAPK11GeneProduct5600 (Entrez Gene)
MAPK12GeneProduct6300 (Entrez Gene)
MAPK13GeneProduct5603 (Entrez Gene)
MAPK14GeneProduct1432 (Entrez Gene)
MIR10AGeneProduct406902 (Entrez Gene)
MIR1224GeneProduct100187716 (Entrez Gene)
MIR127Rna406914 (Entrez Gene)
MIR128-1GeneProduct406915 (Entrez Gene)
MIR128-2GeneProduct406916 (Entrez Gene)
MIR1294GeneProduct100302181 (Entrez Gene)
MIR132GeneProduct406921 (Entrez Gene)
MIR136GeneProduct406927 (Entrez Gene)
MIR16-2GeneProduct406951 (Entrez Gene)
MIR19AGeneProduct406979 (Entrez Gene)
MIR19B1GeneProduct406980 (Entrez Gene)
MIR19B2GeneProduct406981 (Entrez Gene)
MIR212GeneProduct406994 (Entrez Gene)
MIR30AGeneProduct407029 (Entrez Gene)
MIR30EGeneProduct407034 (Entrez Gene)
MIR338GeneProduct442906 (Entrez Gene)
MIR370GeneProduct442915 (Entrez Gene)
MIR409GeneProduct574413 (Entrez Gene)
MIR431Rna574038 (Entrez Gene)
MIR433Rna574034 (Entrez Gene)
MIR4448GeneProduct100616127 (Entrez Gene)
MIR485GeneProduct574436 (Entrez Gene)
MIR873GeneProduct100126316 (Entrez Gene)
MIRLET7GGeneProduct406890 (Entrez Gene)
Oxidative PhosphorylationPathwayWP111 (WikiPathways)
PINK1GeneProduct65018 (Entrez Gene)
ParkinGeneProduct5071 (Entrez Gene)
ROSMetabolite29191 (ChEBI)
SEPT5GeneProduct5413 (Entrez Gene)
SNCAGeneProduct6622 (Entrez Gene)
SNCAIPGeneProduct9627 (Entrez Gene)
SYT11GeneProduct23208 (Entrez Gene)
THGeneProduct7054 (Entrez Gene)
UBA1GeneProduct7317 (Entrez Gene)
UBA7GeneProduct7318 (Entrez Gene)
UBBGeneProduct7314 (Entrez Gene)
UBE2G1GeneProduct7326 (Entrez Gene)
UBE2G2GeneProduct7327 (Entrez Gene)
UBE2J1GeneProduct51465 (Entrez Gene)
UBE2J2GeneProduct118424 (Entrez Gene)
UBE2L3GeneProduct7332 (Entrez Gene)
UBE2L6GeneProduct9246 (Entrez Gene)
UCHL1GeneProduct7345 (Entrez Gene)
WNT SignalingPathwayWP399 (WikiPathways)

Annotated Interactions

No annotated interactions

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