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| Home > Publications Database > Parkin cooperates with GDNF/RET signaling to prevent dopaminergic neuron degeneration. > print |
| 001 | 137919 | ||
| 005 | 20240321220335.0 | ||
| 024 | 7 | _ | |a 10.1172/JCI79300 |2 doi |
| 024 | 7 | _ | |a pmid:25822020 |2 pmid |
| 024 | 7 | _ | |a pmc:PMC4611569 |2 pmc |
| 024 | 7 | _ | |a 0021-9738 |2 ISSN |
| 024 | 7 | _ | |a 1558-8238 |2 ISSN |
| 024 | 7 | _ | |a altmetric:3854816 |2 altmetric |
| 037 | _ | _ | |a DZNE-2020-04241 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Meka, Durga Praveen |b 0 |
| 245 | _ | _ | |a Parkin cooperates with GDNF/RET signaling to prevent dopaminergic neuron degeneration. |
| 260 | _ | _ | |a Ann Arbor, Mich. |c 2015 |b ASCJ |
| 264 | _ | 1 | |3 online |2 Crossref |b American Society for Clinical Investigation |c 2015-03-30 |
| 264 | _ | 1 | |3 print |2 Crossref |b American Society for Clinical Investigation |c 2015-05-01 |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1588667160_1064 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a Parkin and the glial cell line-derived neurotrophic factor (GDNF) receptor RET have both been independently linked to the dopaminergic neuron degeneration that underlies Parkinson's disease (PD). In the present study, we demonstrate that there is genetic crosstalk between parkin and the receptor tyrosine kinase RET in two different mouse models of PD. Mice lacking both parkin and RET exhibited accelerated dopaminergic cell and axonal loss compared with parkin-deficient animals, which showed none, and RET-deficient mice, in which we found moderate degeneration. Transgenic expression of parkin protected the dopaminergic systems of aged RET-deficient mice. Downregulation of either parkin or RET in neuronal cells impaired mitochondrial function and morphology. Parkin expression restored mitochondrial function in GDNF/RET-deficient cells, while GDNF stimulation rescued mitochondrial defects in parkin-deficient cells. In both cases, improved mitochondrial function was the result of activation of the prosurvival NF-κB pathway, which was mediated by RET through the phosphoinositide-3-kinase (PI3K) pathway. Taken together, these observations indicate that parkin and the RET signaling cascade converge to control mitochondrial integrity and thereby properly maintain substantia nigra pars compacta dopaminergic neurons and their innervation in the striatum. The demonstration of crosstalk between parkin and RET highlights the interplay in the protein network that is altered in PD and suggests potential therapeutic targets and strategies to treat PD. |
| 536 | _ | _ | |a 341 - Molecular Signaling (POF3-341) |0 G:(DE-HGF)POF3-341 |c POF3-341 |f POF III |x 0 |
| 588 | _ | _ | |a Dataset connected to CrossRef, PubMed, |
| 650 | _ | 7 | |a Gdnf protein, mouse |2 NLM Chemicals |
| 650 | _ | 7 | |a Glial Cell Line-Derived Neurotrophic Factor |2 NLM Chemicals |
| 650 | _ | 7 | |a NF-kappa B |2 NLM Chemicals |
| 650 | _ | 7 | |a Recombinant Fusion Proteins |2 NLM Chemicals |
| 650 | _ | 7 | |a Adenosine Triphosphate |0 8L70Q75FXE |2 NLM Chemicals |
| 650 | _ | 7 | |a Ubiquitin-Protein Ligases |0 EC 2.3.2.27 |2 NLM Chemicals |
| 650 | _ | 7 | |a parkin protein |0 EC 2.3.2.27 |2 NLM Chemicals |
| 650 | _ | 7 | |a Phosphatidylinositol 3-Kinases |0 EC 2.7.1.- |2 NLM Chemicals |
| 650 | _ | 7 | |a Proto-Oncogene Proteins c-ret |0 EC 2.7.10.1 |2 NLM Chemicals |
| 650 | _ | 7 | |a Ret protein, mouse |0 EC 2.7.10.1 |2 NLM Chemicals |
| 650 | _ | 2 | |a Adenosine Triphosphate: biosynthesis |2 MeSH |
| 650 | _ | 2 | |a Animals |2 MeSH |
| 650 | _ | 2 | |a Anxiety: genetics |2 MeSH |
| 650 | _ | 2 | |a Cell Line |2 MeSH |
| 650 | _ | 2 | |a Cell Size |2 MeSH |
| 650 | _ | 2 | |a Disease Progression |2 MeSH |
| 650 | _ | 2 | |a Dopaminergic Neurons: pathology |2 MeSH |
| 650 | _ | 2 | |a Exploratory Behavior |2 MeSH |
| 650 | _ | 2 | |a Glial Cell Line-Derived Neurotrophic Factor: deficiency |2 MeSH |
| 650 | _ | 2 | |a Glial Cell Line-Derived Neurotrophic Factor: genetics |2 MeSH |
| 650 | _ | 2 | |a Glial Cell Line-Derived Neurotrophic Factor: physiology |2 MeSH |
| 650 | _ | 2 | |a Mice |2 MeSH |
| 650 | _ | 2 | |a Mice, Knockout |2 MeSH |
| 650 | _ | 2 | |a Mice, Transgenic |2 MeSH |
| 650 | _ | 2 | |a Mitochondria: pathology |2 MeSH |
| 650 | _ | 2 | |a NF-kappa B: physiology |2 MeSH |
| 650 | _ | 2 | |a Nerve Degeneration: pathology |2 MeSH |
| 650 | _ | 2 | |a Parkinsonian Disorders: genetics |2 MeSH |
| 650 | _ | 2 | |a Parkinsonian Disorders: pathology |2 MeSH |
| 650 | _ | 2 | |a Phosphatidylinositol 3-Kinases: physiology |2 MeSH |
| 650 | _ | 2 | |a Proto-Oncogene Proteins c-ret: deficiency |2 MeSH |
| 650 | _ | 2 | |a Proto-Oncogene Proteins c-ret: genetics |2 MeSH |
| 650 | _ | 2 | |a Proto-Oncogene Proteins c-ret: physiology |2 MeSH |
| 650 | _ | 2 | |a Recombinant Fusion Proteins: metabolism |2 MeSH |
| 650 | _ | 2 | |a Rotarod Performance Test |2 MeSH |
| 650 | _ | 2 | |a Signal Transduction |2 MeSH |
| 650 | _ | 2 | |a Substantia Nigra: pathology |2 MeSH |
| 650 | _ | 2 | |a Ubiquitin-Protein Ligases: deficiency |2 MeSH |
| 650 | _ | 2 | |a Ubiquitin-Protein Ligases: genetics |2 MeSH |
| 650 | _ | 2 | |a Ubiquitin-Protein Ligases: physiology |2 MeSH |
| 700 | 1 | _ | |a Müller-Rischart, Anne Kathrin |0 P:(DE-2719)9000425 |b 1 |u dzne |
| 700 | 1 | _ | |a Nidadavolu, Prakash |b 2 |
| 700 | 1 | _ | |a Mohammadi, Behnam |b 3 |
| 700 | 1 | _ | |a Motori, Elisa |b 4 |
| 700 | 1 | _ | |a Ponna, Srinivas Kumar |b 5 |
| 700 | 1 | _ | |a Aboutalebi, Helia |0 P:(DE-HGF)0 |b 6 |
| 700 | 1 | _ | |a Bassal, Mahmoud |0 P:(DE-HGF)0 |b 7 |
| 700 | 1 | _ | |a Annamneedi, Anil |b 8 |
| 700 | 1 | _ | |a Finckh, Barbara |b 9 |
| 700 | 1 | _ | |a Miesbauer, Margit |0 P:(DE-HGF)0 |b 10 |
| 700 | 1 | _ | |a Rotermund, Natalie |b 11 |
| 700 | 1 | _ | |a Lohr, Christian |b 12 |
| 700 | 1 | _ | |a Tatzelt, Jörg |0 P:(DE-HGF)0 |b 13 |
| 700 | 1 | _ | |a Winklhofer, Konstanze F |0 P:(DE-2719)9000369 |b 14 |u dzne |
| 700 | 1 | _ | |a Kramer, Edgar R |0 P:(DE-HGF)0 |b 15 |e Corresponding author |
| 773 | 1 | 8 | |a 10.1172/jci79300 |b : American Society for Clinical Investigation, 2015-03-30 |n 5 |p 1873-1885 |3 journal-article |2 Crossref |t Journal of Clinical Investigation |v 125 |y 2015 |x 0021-9738 |
| 773 | _ | _ | |a 10.1172/JCI79300 |g Vol. 125, no. 5, p. 1873 - 1885 |0 PERI:(DE-600)2018375-6 |n 5 |q 125:5<1873 - 1885 |p 1873-1885 |t The journal of clinical investigation |v 125 |y 2015 |x 0021-9738 |
| 856 | 7 | _ | |2 Pubmed Central |u http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4611569 |
| 909 | C | O | |o oai:pub.dzne.de:137919 |p VDB |
| 910 | 1 | _ | |a Deutsches Zentrum für Neurodegenerative Erkrankungen |0 I:(DE-588)1065079516 |k DZNE |b 1 |6 P:(DE-2719)9000425 |
| 910 | 1 | _ | |a Deutsches Zentrum für Neurodegenerative Erkrankungen |0 I:(DE-588)1065079516 |k DZNE |b 14 |6 P:(DE-2719)9000369 |
| 913 | 1 | _ | |a DE-HGF |b Forschungsbereich Gesundheit |l Erkrankungen des Nervensystems |1 G:(DE-HGF)POF3-340 |0 G:(DE-HGF)POF3-341 |2 G:(DE-HGF)POF3-300 |v Molecular Signaling |x 0 |
| 914 | 1 | _ | |y 2015 |
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| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0200 |2 StatID |b SCOPUS |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0300 |2 StatID |b Medline |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0310 |2 StatID |b NCBI Molecular Biology Database |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0320 |2 StatID |b PubMed Central |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0600 |2 StatID |b Ebsco Academic Search |
| 915 | _ | _ | |a Peer Review |0 StatID:(DE-HGF)0030 |2 StatID |b ASC |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0199 |2 StatID |b Clarivate Analytics Master Journal List |
| 915 | _ | _ | |a WoS |0 StatID:(DE-HGF)0110 |2 StatID |b Science Citation Index |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0150 |2 StatID |b Web of Science Core Collection |
| 915 | _ | _ | |a WoS |0 StatID:(DE-HGF)0111 |2 StatID |b Science Citation Index Expanded |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)1030 |2 StatID |b Current Contents - Life Sciences |
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| 980 | _ | _ | |a VDB |
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| 980 | _ | _ | |a UNRESTRICTED |
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