Parkinsons Disease Pathway (Mus musculus)

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3, 5, 7, 10, 21417, 18, 249, 191520ProteinUbiquitin pathway componentsXO-glycosylationOxidative StressLewy BodyDdcApoptosis PathwayROSEprsSlc6a3Uchl1Park2Snca11ThL-TyrosineL-DOPADopamineDopamineLrrk2Pink113Park723Htra2Cycs Gpr37Sept5SncaipUbbUba1Uba7Ube2l3 Ube2l6 Ube2j2Ube2g1Ube2g2Ube2j1 Targets for Ub degradationAtxn22, 12, 14, 15Syt11Ccne1Ccne2SncaSncaipMapk12Mapk11Mapk14Mapk13XXAggregationCell DeathDopamine oxidationUb Proteosome System DysfunctionToxicityDopaminergic NeuronMitochondrial Dysfunction1, 8Oxidative Phosphorylation(Electron Transport Chain)Apoptosis PathwayCell Death22Casp6Casp9Casp2CycsCasp7Casp3Apaf1XMAPK SignalingWNT SignalingXParkinson's disease genes: pathogenic mutationsBlock of normal function for mutated genesIndirect actionmmu-mir-132mmu-mir-19ammu-mir-485mmu-mir-127mmu-mir-128-1mmu-mir-128-2mmu-mir-409mmu-let-7gmmu-mir-433mmu-mir-370mmu-mir-873ammu-mir-431mmu-mir-136 mmu-mir-212mmu-mir-10ammu-mir-1224miRNA differentially expressed in PD (measured in cerebrospinal fluid)mmu-mir-338mmu-mir-16-2 mmu-mir-30e mmu-mir-30amiRNA differentially expressed in PD (measured in blood serum)Based on Tables 1, 2 and S3 from Burgos et al, PLoS ONE 2014 May.mmu-mir-50316miRNA differentially expressed in PD vs PD-Dementia (measured in blood serum)mmu-mir-503mmu-mir-34c mmu-mir-34bmmu-mir-34cmmu-mir-34bmmu-mir-195a mmu-mir-195ammu-mir-26bmmu-mir-375mmu-mir-375mmu-mir-26b19mmu-mir-26b


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.

This is an updated copy of the human parkinson disease pathway (WP2371).


Sources: wikipedia, Quigen, and KEGG.

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Bibliography

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

History

View all...
CompareRevisionActionTimeUserComment
107203view14:29, 17 September 2019MaintBotChEBI identifier normalization
97511view13:41, 24 May 2018Mick Eikelhofedit annotation for ROS
87401view11:05, 22 July 2016MaintBotadded missing graphids
85261view10:12, 4 May 2016FehrhartModified description
85260view10:12, 4 May 2016FehrhartOntology Term : 'neuron' added !
85259view10:11, 4 May 2016FehrhartOntology Term : 'neurodegenerative disease' added !
85258view10:11, 4 May 2016FehrhartOntology Term : 'Lewy body dementia' added !
85257view10:10, 4 May 2016FehrhartOntology Term : 'Parkinson's disease' added !
85256view10:10, 4 May 2016FehrhartOntology Term : 'Parkinson disease pathway' added !
85255view10:10, 4 May 2016FehrhartOntology Term : 'neurodegenerative disease pathway' added !
85254view10:08, 4 May 2016FehrhartNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
Apaf1GeneProductENSMUSG00000019979 (Ensembl)
Apoptosis PathwayPathwayWP1254 (WikiPathways)
Atxn2GeneProductENSMUSG00000042605 (Ensembl)
Casp2GeneProductENSMUSG00000029863 (Ensembl)
Casp3GeneProductENSMUSG00000031628 (Ensembl)
Casp6GeneProductENSMUSG00000027997 (Ensembl)
Casp7GeneProductENSMUSG00000025076 (Ensembl)
Casp9GeneProductENSMUSG00000028914 (Ensembl)
Ccne1GeneProductENSMUSG00000002068 (Ensembl)
Ccne2GeneProductENSMUSG00000028212 (Ensembl)
Cycs GeneProductENSMUSG00000063694 (Ensembl)
CycsGeneProductENSMUSG00000063694 (Ensembl)
DdcGeneProductENSMUSG00000020182 (Ensembl)
DopamineMetaboliteC03758 (KEGG Compound)
EprsGeneProductENSMUSG00000026615 (Ensembl)
Gpr37GeneProductENSMUSG00000039904 (Ensembl)
Htra2GeneProductENSMUSG00000068329 (Ensembl)
L-DOPAMetaboliteC00355 (KEGG Compound)
L-TyrosineMetaboliteC00082 (KEGG Compound)
Lrrk2GeneProductENSMUSG00000036273 (Ensembl)
MAPK SignalingPathwayWP493 (WikiPathways)
Mapk11GeneProductENSMUSG00000053137 (Ensembl)
Mapk12GeneProductENSMUSG00000022610 (Ensembl)
Mapk13GeneProductENSMUSG00000004864 (Ensembl)
Mapk14GeneProductENSMUSG00000053436 (Ensembl)
Oxidative Phosphorylation (Electron Transport Chain)PathwayWP295 (WikiPathways)
Park2GeneProductENSMUSG00000023826 (Ensembl)
Park7GeneProductENSMUSG00000028964 (Ensembl)
Pink1GeneProductENSMUSG00000028756 (Ensembl)
ROSMetaboliteCHEBI:26523 (ChEBI)
Sept5GeneProductENSMUSG00000072214 (Ensembl)
Slc6a3GeneProductENSMUSG00000021609 (Ensembl)
SncaGeneProductENSMUSG00000025889 (Ensembl)
SncaipGeneProductENSMUSG00000024534 (Ensembl)
Syt11GeneProductENSMUSG00000068923 (Ensembl)
ThGeneProductENSMUSG00000000214 (Ensembl)
Uba1GeneProductENSMUSG00000001924 (Ensembl)
Uba7GeneProductENSMUSG00000032596 (Ensembl)
UbbGeneProductENSMUSG00000019505 (Ensembl)
Ube2g1GeneProductENSMUSG00000020794 (Ensembl)
Ube2g2GeneProductENSMUSG00000009293 (Ensembl)
Ube2j1 GeneProductENSMUSG00000028277 (Ensembl)
Ube2j2GeneProductENSMUSG00000023286 (Ensembl)
Ube2l3 GeneProductENSMUSG00000038965 (Ensembl)
Ube2l6 GeneProductENSMUSG00000027078 (Ensembl)
Uchl1GeneProductENSMUSG00000029223 (Ensembl)
WNT SignalingPathwayWP723 (WikiPathways)
mmu-let-7gRnaMI0000137 (miRBase Sequence)
mmu-mir-10aRnaMI0000685 (miRBase Sequence)
mmu-mir-1224RnaMI0004118 (miRBase Sequence)
mmu-mir-127RnaMI0000154 (miRBase Sequence)
mmu-mir-128-1RnaMI0000155 (miRBase Sequence)
mmu-mir-128-2Rnammu-mir-128-2 (miRBase Sequence)
mmu-mir-132RnaMI0000158 (miRBase Sequence)
mmu-mir-136 RnaMI0000162 (miRBase Sequence)
mmu-mir-16-2 RnaMI0000566 (miRBase Sequence)
mmu-mir-195a RnaMI0000237 (miRBase Sequence)
mmu-mir-195aRnaMI0000237 (miRBase Sequence)
mmu-mir-19aRnaMI0000688 (miRBase Sequence)
mmu-mir-212RnaMI0000696 (miRBase Sequence)
mmu-mir-26bRnaMI0000575 (miRBase Sequence)
mmu-mir-30aRnaMI0000144 (miRBase Sequence)
mmu-mir-30e RnaMI0000259 (miRBase Sequence)
mmu-mir-338RnaMI0000619 (miRBase Sequence)
mmu-mir-34bRnaMI0000404 (miRBase Sequence)
mmu-mir-34c RnaMI0000403 (miRBase Sequence)
mmu-mir-34cRnaMI0000403 (miRBase Sequence)
mmu-mir-370RnaMI0001165 (miRBase Sequence)
mmu-mir-375RnaMI0000792 (miRBase Sequence)
mmu-mir-409RnaMI0001160 (miRBase Sequence)
mmu-mir-431RnaMI0001524 (miRBase Sequence)
mmu-mir-433RnaMI0001525 (miRBase Sequence)
mmu-mir-485RnaMI0003492 (miRBase Sequence)
mmu-mir-503RnaMI0003538 (miRBase Sequence)
mmu-mir-503Rnammu-mir-503 (miRBase Sequence)
mmu-mir-873aRnaMI0005550 (miRBase Sequence)

Annotated Interactions

No annotated interactions

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