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Parkinson Disease

Disease ID:732
Name:Parkinson Disease
Associated with:5 targets
1 immuno-relevant target
Parkinson's disease
Database Links
Disease Ontology: DOID:14330
OMIM: 168600


Role:  Since KCa2.3 channels regulate the firing frequency of dopaminergic neurons, KCa2.3 blockers have been proposed for the treatment of Parkinson disease.
Drugs:  Apamin and N-methyl-laudanosine (experimentally)
Side effects:  High doses of apamin induce seizures and lead to Purkinje cell degeneration in the cerebellum.
Therapeutic use:  KCa2.3 blockers have been proposed for the treatment of Parkinson disease.
References:  2,10-12
Nuclear receptor related 1
Comments:  Some links suggested in individuals with familial Parkinson disease but the same mutations are not confirmed in other studies.
References:  3-4,6
regulator of G-protein signaling 4
References:  5,9
regulator of G-protein signaling 6
Role:  RGS6 has a neuroprotective effect which is critical for survival and maintenance of the ventral substantia nigra compacta (vSNc) midbrain dopaminergic neurons that are most affected in Parkinson's disease.
References:  1
regulator of G-protein signaling 10
References:  8


No ligand related data available for Parkinson Disease


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1. Bifsha P, Yang J, Fisher RA, Drouin J. (2014) Rgs6 is required for adult maintenance of dopaminergic neurons in the ventral substantia nigra. PLoS Genet, 10 (12): e1004863. [PMID:25501001]

2. Blank T, Nijholt I, Kye MJ, Spiess J. (2004) Small conductance Ca2+-activated K+ channels as targets of CNS drug development. Curr Drug Targets CNS Neurol Disord, 3 (3): 161-7. [PMID:15180477]

3. Hering R, Petrovic S, Mietz EM, Holzmann C, Berg D, Bauer P, Woitalla D, Müller T, Berger K, Krüger R, Riess O. (2004) Extended mutation analysis and association studies of Nurr1 (NR4A2) in Parkinson disease. Neurology, 62 (7): 1231-2. [PMID:15079038]

4. Ibáñez P, Lohmann E, Pollak P, Durif F, Tranchant C, Agid Y, Dürr A, Brice A, French Parkinson's Disease Genetics Study Group. (2004) Absence of NR4A2 exon 1 mutations in 108 families with autosomal dominant Parkinson disease. Neurology, 62 (11): 2133-4. [PMID:15184637]

5. Ko WK, Martin-Negrier ML, Bezard E, Crossman AR, Ravenscroft P. (2014) RGS4 is involved in the generation of abnormal involuntary movements in the unilateral 6-OHDA-lesioned rat model of Parkinson's disease. Neurobiol Dis, 70: 138-48. [PMID:24969021]

6. Le WD, Xu P, Jankovic J, Jiang H, Appel SH, Smith RG, Vassilatis DK. (2003) Mutations in NR4A2 associated with familial Parkinson disease. Nat Genet, 33 (1): 85-9. [PMID:12496759]

7. Lee JK, Chung J, McAlpine FE, Tansey MG. (2011) Regulator of G-protein signaling-10 negatively regulates NF-κB in microglia and neuroprotects dopaminergic neurons in hemiparkinsonian rats. J Neurosci, 31 (33): 11879-88. [PMID:21849548]

8. Lee JK, McCoy MK, Harms AS, Ruhn KA, Gold SJ, Tansey MG. (2008) Regulator of G-protein signaling 10 promotes dopaminergic neuron survival via regulation of the microglial inflammatory response. J Neurosci, 28 (34): 8517-28. [PMID:18716210]

9. Lerner TN, Kreitzer AC. (2012) RGS4 is required for dopaminergic control of striatal LTD and susceptibility to parkinsonian motor deficits. Neuron, 73 (2): 347-59. [PMID:22284188]

10. Mourre C, Fournier C, Soumireu-Mourat B. (1997) Apamin, a blocker of the calcium-activated potassium channel, induces neurodegeneration of Purkinje cells exclusively. Brain Res, 778 (2): 405-8. [PMID:9459560]

11. Waroux O, Massotte L, Alleva L, Graulich A, Thomas E, Liégeois JF, Scuvée-Moreau J, Seutin V. (2005) SK channels control the firing pattern of midbrain dopaminergic neurons in vivo. Eur J Neurosci, 22 (12): 3111-21. [PMID:16367777]

12. Wulff H, Kolski-Andreaco A, Sankaranarayanan A, Sabatier JM, Shakkottai V. (2007) Modulators of small- and intermediate-conductance calcium-activated potassium channels and their therapeutic indications. Curr Med Chem, 14 (13): 1437-57. [PMID:17584055]