KEGG PATHWAY: map05012

PATHWAY: map05012

Entry

map05012                    Pathway

Name

Parkinson disease

Description

Parkinson disease (PD) is a progressive neurodegenerative movement disorder that results primarily from the death of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Both environmental factors and mutations in familial PD-linked genes such as SNCA, Parkin, DJ-1, PINK1 and LRRK2 are associated with PD pathogenesis. These pathogenic mutations and environmental factors are known to cause disease due to oxidative stress, intracellular Ca2+ homeostasis impairment, mitochondrial dysfunctions and altered protein handling compromising key roles of DA neuronal function and survival. The demise of DA neurons located in the SNc leads to a drop in the dopaminergic input to the striatum, which is hypothesized to impede movement by inducing hypo and hyper activity in striatal spiny projection neurons (SPNs) of the direct (dSPNs) and indirect (iSPNs) pathways in the basal ganglia, respectively.

Class

Human Diseases; Neurodegenerative disease

Pathway map

map05012

Parkinson disease

Disease

H00057

Parkinson disease

Reference

PMID:16495942

Authors

Abou-Sleiman PM, Muqit MM, Wood NW

Title

Expanding insights of mitochondrial dysfunction in Parkinson's disease.

Journal

Nat Rev Neurosci 7:207-19 (2006)
DOI:10.1038/nrn1868

Reference

PMID:12938733

Authors

Lim KL, Lim TM

Title

Molecular mechanisms of neurodegeneration in Parkinson's disease: clues from Mendelian syndromes.

Journal

IUBMB Life 55:315-22 (2003)
DOI:10.1080/1521654031000153030

Reference

PMID:26501339

Authors

Bobela W, Aebischer P, Schneider BL

Title

Alphalpha-Synuclein as a Mediator in the Interplay between Aging and Parkinson's Disease.

Journal

Biomolecules 5:2675-700 (2015)
DOI:10.3390/biom5042675

Reference

PMID:15767499

Authors

Eriksen JL, Wszolek Z, Petrucelli L

Title

Molecular pathogenesis of Parkinson disease.

Journal

Arch Neurol 62:353-7 (2005)
DOI:10.1001/archneur.62.3.353

Reference

PMID:16972273

Authors

Olanow CW, McNaught KS

Title

Ubiquitin-proteasome system and Parkinson's disease.

Journal

Mov Disord 21:1806-23 (2006)
DOI:10.1002/mds.21013

Reference

PMID:18047737

Authors

Lim KL, Tan JM

Title

Role of the ubiquitin proteasome system in Parkinson's disease.

Journal

BMC Biochem 8 Suppl 1:S13 (2007)
DOI:10.1186/1471-2091-8-S1-S13

Reference

PMID:29090092

Authors

Maiti P, Manna J, Dunbar GL

Title

Current understanding of the molecular mechanisms in Parkinson's disease: Targets for potential treatments.

Journal

Transl Neurodegener 6:28 (2017)
DOI:10.1186/s40035-017-0099-z

Reference

PMID:12814656

Authors

Dev KK, van der Putten H, Sommer B, Rovelli G

Title

Part I: parkin-associated proteins and Parkinson's disease.

Journal

Neuropharmacology 45:1-13 (2003)
DOI:10.1016/s0028-3908(02)00337-4

Reference

PMID:20495568

Authors

Obeso JA, Rodriguez-Oroz MC, Goetz CG, Marin C, Kordower JH, Rodriguez M, Hirsch EC, Farrer M, Schapira AH, Halliday G

Title

Missing pieces in the Parkinson's disease puzzle.

Journal

Nat Med 16:653-61 (2010)
DOI:10.1038/nm.2165

Reference

PMID:24781149

Authors

Cali T, Ottolini D, Brini M

Title

Calcium signaling in Parkinson's disease.

Journal

Cell Tissue Res 357:439-54 (2014)
DOI:10.1007/s00441-014-1866-0

Reference

PMID:19230774

Authors

Bezprozvanny I

Title

Calcium signaling and neurodegenerative diseases.

Journal

Trends Mol Med 15:89-100 (2009)
DOI:10.1016/j.molmed.2009.01.001

Reference

PMID:28468938

Authors

Zaichick SV, McGrath KM, Caraveo G

Title

The role of Ca(2+) signaling in Parkinson's disease.

Journal

Dis Model Mech 10:519-535 (2017)
DOI:10.1242/dmm.028738

Reference

PMID:28838811

Authors

Ludtmann MHR, Abramov AY

Title

Mitochondrial calcium imbalance in Parkinson's disease.

Journal

Neurosci Lett 663:86-90 (2018)
DOI:10.1016/j.neulet.2017.08.044

Reference

PMID:19663908

Authors

Sandebring A, Dehvari N, Perez-Manso M, Thomas KJ, Karpilovski E, Cookson MR, Cowburn RF, Cedazo-Minguez A

Title

Parkin deficiency disrupts calcium homeostasis by modulating phospholipase C signalling.

Journal

FEBS J 276:5041-52 (2009)
DOI:10.1111/j.1742-4658.2009.07201.x

Reference

PMID:23352769

Authors

Mercado G, Valdes P, Hetz C

Title

An ERcentric view of Parkinson's disease.

Journal

Trends Mol Med 19:165-75 (2013)
DOI:10.1016/j.molmed.2012.12.005

Reference

PMID:27103567

Authors

Mercado G, Castillo V, Soto P, Sidhu A

Title

ER stress and Parkinson's disease: Pathological inputs that converge into the secretory pathway.

Journal

Brain Res 1648:626-632 (2016)
DOI:10.1016/j.brainres.2016.04.042

Reference

PMID:26297973

Authors

Tsujii S, Ishisaka M, Hara H

Title

Modulation of endoplasmic reticulum stress in Parkinson's disease.

Journal

Eur J Pharmacol 765:154-6 (2015)
DOI:10.1016/j.ejphar.2015.08.033

Reference

PMID:31100053

Authors

Shah A, Chao J, Legido-Quigley C, Chang RC

Title

Oxyresveratrol exerts ATF4- and Grp78-mediated neuroprotection against endoplasmic reticulum stress in experimental Parkinson's disease.

Journal

Nutr Neurosci 1-16 (2019)
DOI:10.1080/1028415X.2019.1613764

Reference

PMID:24548101

Authors

Segura-Aguilar J, Paris I, Munoz P, Ferrari E, Zecca L, Zucca FA

Title

Protective and toxic roles of dopamine in Parkinson's disease.

Journal

J Neurochem 129:898-915 (2014)
DOI:10.1111/jnc.12686

Reference

PMID:31587020

Authors

Jesko H, Lenkiewicz AM, Wilkaniec A, Adamczyk A

Title

The interplay between parkin and alpha-synuclein; possible implications for the pathogenesis of Parkinson's disease.

Journal

Acta Neurobiol Exp (Wars) 79:276-289 (2019)

Reference

PMID:15189334

Authors

Perez RG, Hastings TG

Title

Could a loss of alpha-synuclein function put dopaminergic neurons at risk?

Journal

J Neurochem 89:1318-24 (2004)
DOI:10.1111/j.1471-4159.2004.02423.x

Reference

PMID:26487845

Authors

Segura-Aguilar J

Title

A new mechanism for protection of dopaminergic neurons mediated by astrocytes.

Journal

Neural Regen Res 10:1225-7 (2015)
DOI:10.4103/1673-5374.162750

Reference

PMID:27546335

Authors

Bose A, Beal MF

Title

Mitochondrial dysfunction in Parkinson's disease.

Journal

J Neurochem 139 Suppl 1:216-231 (2016)
DOI:10.1111/jnc.13731

Reference

PMID:27581196

Authors

Cieri D, Brini M, Cali T

Title

Emerging (and converging) pathways in Parkinson's disease: keeping mitochondrial wellness.

Journal

Biochem Biophys Res Commun 483:1020-1030 (2017)
DOI:10.1016/j.bbrc.2016.08.153

Reference

PMID:27829983

Authors

Mack JM, Schamne MG, Sampaio TB, Pertile RA, Fernandes PA, Markus RP, Prediger RD

Title

Melatoninergic System in Parkinson's Disease: From Neuroprotection to the Management of Motor and Nonmotor Symptoms.

Journal

Oxid Med Cell Longev 2016:3472032 (2016)
DOI:10.1155/2016/3472032

Reference

PMID:21674642

Authors

Cali T, Ottolini D, Brini M

Title

Mitochondria, calcium, and endoplasmic reticulum stress in Parkinson's disease.

Journal

Biofactors 37:228-40 (2011)
DOI:10.1002/biof.159

Reference

PMID:24522549

Authors

Gaki GS, Papavassiliou AG

Title

Oxidative stress-induced signaling pathways implicated in the pathogenesis of Parkinson's disease.

Journal

Neuromolecular Med 16:217-30 (2014)
DOI:10.1007/s12017-014-8294-x

Reference

PMID:25761946

Authors

Franco-Iborra S, Vila M, Perier C

Title

The Parkinson Disease Mitochondrial Hypothesis: Where Are We at?

Journal

Neuroscientist 22:266-77 (2016)
DOI:10.1177/1073858415574600

Reference

PMID:22926193

Authors

de Vries RL, Przedborski S

Title

Mitophagy and Parkinson's disease: be eaten to stay healthy.

Journal

Mol Cell Neurosci 55:37-43 (2013)
DOI:10.1016/j.mcn.2012.07.008

Reference

PMID:20736035

Authors

Deas E, Wood NW, Plun-Favreau H

Title

Mitophagy and Parkinson's disease: the PINK1-parkin link.

Journal

Biochim Biophys Acta 1813:623-33 (2011)
DOI:10.1016/j.bbamcr.2010.08.007

Reference

PMID:25611507

Authors

Pickrell AM, Youle RJ

Title

The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson's disease.

Journal

Neuron 85:257-73 (2015)
DOI:10.1016/j.neuron.2014.12.007

Reference

PMID:27911343

Authors

Truban D, Hou X, Caulfield TR, Fiesel FC, Springer W

Title

PINK1, Parkin, and Mitochondrial Quality Control: What can we Learn about Parkinson's Disease Pathobiology?

Journal

J Parkinsons Dis 7:13-29 (2017)
DOI:10.3233/JPD-160989

Reference

PMID:28823929

Authors

Biosa A, Sandrelli F, Beltramini M, Greggio E, Bubacco L, Bisaglia M

Title

Recent findings on the physiological function of DJ-1: Beyond Parkinson's disease.

Journal

Neurobiol Dis 108:65-72 (2017)
DOI:10.1016/j.nbd.2017.08.005

Reference

PMID:29147906

Authors

Oh SE, Mouradian MM

Title

Regulation of Signal Transduction by DJ-1.

Journal

Adv Exp Med Biol 1037:97-131 (2017)
DOI:10.1007/978-981-10-6583-5_8

Reference

PMID:31054074

Authors

Dolgacheva LP, Berezhnov AV, Fedotova EI, Zinchenko VP, Abramov AY

Title

Role of DJ-1 in the mechanism of pathogenesis of Parkinson's disease.

Journal

J Bioenerg Biomembr 51:175-188 (2019)
DOI:10.1007/s10863-019-09798-4

Reference

PMID:30370500

Authors

Melo TQ, Copray SJCVM, Ferrari MFR

Title

Alpha-Synuclein Toxicity on Protein Quality Control, Mitochondria and Endoplasmic Reticulum.

Journal

Neurochem Res 43:2212-2223 (2018)
DOI:10.1007/s11064-018-2673-x

Reference

PMID:30937538

Authors

Zhai S, Shen W, Graves SM, Surmeier DJ

Title

Dopaminergic modulation of striatal function and Parkinson's disease.

Journal

J Neural Transm (Vienna) 126:411-422 (2019)
DOI:10.1007/s00702-019-01997-y

Reference

PMID:29720658

Authors

Parker JG, Marshall JD, Ahanonu B, Wu YW, Kim TH, Grewe BF, Zhang Y, Li JZ, Ding JB, Ehlers MD, Schnitzer MJ

Title

Diametric neural ensemble dynamics in parkinsonian and dyskinetic states.

Journal

Nature 557:177-182 (2018)
DOI:10.1038/s41586-018-0090-6

Related
pathway

map00190

Oxidative phosphorylation

map00350

Tyrosine metabolism

map03050

Proteasome

map04020

Calcium signaling pathway

map04120

Ubiquitin mediated proteolysis

map04137

Mitophagy - animal

map04141

Protein processing in endoplasmic reticulum

map04210

Apoptosis

map04728

Dopaminergic synapse

KO pathway

ko05012

All links

Chemical substance (26)   
   KEGG COMPOUND (26)   
Gene (501070)   
   KEGG ORTHOLOGY (209)   
   RefGene (500861)   
Literature (38)   
   PubMed (38)   
All databases (501134)   

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