ArticleThe Journal of clinical investigation2015
Parkin cooperates with GDNF/RET signaling to prevent dopaminergic neuron degeneration.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 80 citations in OpenAlex.
- Oleuropein Attenuates 6-Hydroxydopamine-Induced Cytotoxicity Through Redox Regulation in Differentiated Dopaminergic Neurons: Potential Involvement of RET-Associated Signalling.International journal of molecular sciences · 2026Article
- Article
- Integrating artificial intelligence and optogenetics for Parkinson's disease diagnosis and therapeutics in male mice.Nature communications · 2025Article
- Unlocking Alzheimer's Disease: The Role of BDNF Signaling in Neuropathology and Treatment.Neuromolecular medicine · 2025Review
- Reactive Astrocytes Release GDNF to Promote Brain Recovery and Neuronal Survival Following Ischemic Stroke.Neurochemical research · 2025Article
- Mitochondria-targeted nanovesicles for ursodeoxycholic acid delivery to combat neurodegeneration by ameliorating mitochondrial dysfunction.Journal of nanobiotechnology · 2025Article
- Effects of glial-derived neurotrophic factor on remodeling and mitochondrial function in human airway smooth muscle cells.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Selpercatinib combination with the mitochondria-targeted antioxidant MitoQ effectively suppresses RET-mutant thyroid cancer.NPJ precision oncology · 2024Article
- NEMO reshapes the α-Synuclein aggregate interface and acts as an autophagy adapter by co-condensation with p62.Nature communications · 2023Article
- Analysis of Acute and Chronic Methamphetamine Treatment in Mice on Gdnf System Expression Reveals a Potential Mechanism of Schizophrenia Susceptibility.Biomolecules · 2023Article
- Is activation of GDNF/RET signaling the answer for successful treatment of Parkinson's disease? A discussion of data from the culture dish to the clinic.Neural regeneration research · 2022Review
- Obligatory Activation of SRC and JNK by GDNF for Survival and Axonal Outgrowth of Postnatal Intestinal Neurons.Cellular and molecular neurobiology · 2022Article
- Protective Effects of Polysaccharides in Neurodegenerative Diseases.Frontiers in aging neuroscience · 2022Review
- Optogenetic delivery of trophic signals in a genetic model of Parkinson's disease.PLoS genetics · 2021Article
- Mouse Embryonic Stem Cells Expressing GDNF Show Enhanced Dopaminergic Differentiation and Promote Behavioral Recovery After Grafting in Parkinsonian Rats.Frontiers in cell and developmental biology · 2021Article
- Melatonin promotes Schwann cell dedifferentiation and proliferation through the Ras/Raf/ERK and MAPK pathways, and glial cell-derived neurotrophic factor expression.Experimental and therapeutic medicine · 2020Article
- Characterization of a Cul9-Parkin double knockout mouse model for Parkinson's disease.Scientific reports · 2020Article
- RET isoforms contribute differentially to invasive processes in pancreatic ductal adenocarcinoma.Oncogene · 2020Article
- Melatonin and Autophagy in Aging-Related Neurodegenerative Diseases.International journal of molecular sciences · 2020Review
- RET Receptor Tyrosine Kinase: Role in Neurodegeneration, Obesity, and Cancer.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.