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Parkin cooperates with GDNF/RET signaling to prevent dopaminergic neuron degeneration

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Parkin cooperates with GDNF/RET signaling to prevent dopaminergic neuron degeneration. / Meka, Praveen; Müller-Rischart, Anne Kathrin; Nidadavolu, Prakash; Mohammadi, Behnam; Motori, Elisa; Ponna, Srinivas Kumar; Aboutalebi, Helia; Bassal, Mahmoud; Annamneedi, Anil; Finckh, Barbara; Miesbauer, Margit; Rotermund, Natalie; Lohr, Christian; Tatzelt, Jörg; Winklhofer, Konstanze F; Kramer, Edgar R.

in: J CLIN INVEST, Jahrgang 125, Nr. 5, 05.2015, S. 1873-85.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Meka, P, Müller-Rischart, AK, Nidadavolu, P, Mohammadi, B, Motori, E, Ponna, SK, Aboutalebi, H, Bassal, M, Annamneedi, A, Finckh, B, Miesbauer, M, Rotermund, N, Lohr, C, Tatzelt, J, Winklhofer, KF & Kramer, ER 2015, 'Parkin cooperates with GDNF/RET signaling to prevent dopaminergic neuron degeneration', J CLIN INVEST, Jg. 125, Nr. 5, S. 1873-85. https://doi.org/10.1172/JCI79300

APA

Meka, P., Müller-Rischart, A. K., Nidadavolu, P., Mohammadi, B., Motori, E., Ponna, S. K., Aboutalebi, H., Bassal, M., Annamneedi, A., Finckh, B., Miesbauer, M., Rotermund, N., Lohr, C., Tatzelt, J., Winklhofer, K. F., & Kramer, E. R. (2015). Parkin cooperates with GDNF/RET signaling to prevent dopaminergic neuron degeneration. J CLIN INVEST, 125(5), 1873-85. https://doi.org/10.1172/JCI79300

Vancouver

Meka P, Müller-Rischart AK, Nidadavolu P, Mohammadi B, Motori E, Ponna SK et al. Parkin cooperates with GDNF/RET signaling to prevent dopaminergic neuron degeneration. J CLIN INVEST. 2015 Mai;125(5):1873-85. https://doi.org/10.1172/JCI79300

Bibtex

@article{968bfd24fc0842b1ae23af79039ba313,
title = "Parkin cooperates with GDNF/RET signaling to prevent dopaminergic neuron degeneration",
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.",
keywords = "Adenosine Triphosphate, Animals, Anxiety, Cell Line, Cell Size, Disease Progression, Dopaminergic Neurons, Exploratory Behavior, Glial Cell Line-Derived Neurotrophic Factor, Mice, Mice, Knockout, Mice, Transgenic, Mitochondria, NF-kappa B, Nerve Degeneration, Parkinsonian Disorders, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-ret, Recombinant Fusion Proteins, Rotarod Performance Test, Signal Transduction, Substantia Nigra, Ubiquitin-Protein Ligases",
author = "Praveen Meka and M{\"u}ller-Rischart, {Anne Kathrin} and Prakash Nidadavolu and Behnam Mohammadi and Elisa Motori and Ponna, {Srinivas Kumar} and Helia Aboutalebi and Mahmoud Bassal and Anil Annamneedi and Barbara Finckh and Margit Miesbauer and Natalie Rotermund and Christian Lohr and J{\"o}rg Tatzelt and Winklhofer, {Konstanze F} and Kramer, {Edgar R}",
year = "2015",
month = may,
doi = "10.1172/JCI79300",
language = "English",
volume = "125",
pages = "1873--85",
journal = "J CLIN INVEST",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "5",

}

RIS

TY - JOUR

T1 - Parkin cooperates with GDNF/RET signaling to prevent dopaminergic neuron degeneration

AU - Meka, Praveen

AU - Müller-Rischart, Anne Kathrin

AU - Nidadavolu, Prakash

AU - Mohammadi, Behnam

AU - Motori, Elisa

AU - Ponna, Srinivas Kumar

AU - Aboutalebi, Helia

AU - Bassal, Mahmoud

AU - Annamneedi, Anil

AU - Finckh, Barbara

AU - Miesbauer, Margit

AU - Rotermund, Natalie

AU - Lohr, Christian

AU - Tatzelt, Jörg

AU - Winklhofer, Konstanze F

AU - Kramer, Edgar R

PY - 2015/5

Y1 - 2015/5

N2 - 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.

AB - 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.

KW - Adenosine Triphosphate

KW - Animals

KW - Anxiety

KW - Cell Line

KW - Cell Size

KW - Disease Progression

KW - Dopaminergic Neurons

KW - Exploratory Behavior

KW - Glial Cell Line-Derived Neurotrophic Factor

KW - Mice

KW - Mice, Knockout

KW - Mice, Transgenic

KW - Mitochondria

KW - NF-kappa B

KW - Nerve Degeneration

KW - Parkinsonian Disorders

KW - Phosphatidylinositol 3-Kinases

KW - Proto-Oncogene Proteins c-ret

KW - Recombinant Fusion Proteins

KW - Rotarod Performance Test

KW - Signal Transduction

KW - Substantia Nigra

KW - Ubiquitin-Protein Ligases

U2 - 10.1172/JCI79300

DO - 10.1172/JCI79300

M3 - SCORING: Journal article

C2 - 25822020

VL - 125

SP - 1873

EP - 1885

JO - J CLIN INVEST

JF - J CLIN INVEST

SN - 0021-9738

IS - 5

ER -