Tesseur, I;
Nguyen, A;
Chang, B;
Li, L;
Woodling, NS;
Wyss-Coray, T;
Luo, J;
(2017)
Deficiency in Neuronal TGF-β Signaling Leads to Nigrostriatal Degeneration and Activation of TGF-β Signaling Protects against MPTP Neurotoxicity in Mice.
The Journal of Neuroscience
, 37
(17)
pp. 4584-4592.
10.1523/JNEUROSCI.2952-16.2017.
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Abstract
Transforming growth factor-β (TGF-β) plays an important role in the development and maintenance of embryonic dopaminergic (DA) neurons in the midbrain. To study the function of TGF-β signaling in the adult nigrostriatal system, we generated transgenic mice with reduced TGF-β signaling in mature neurons. These mice display age-related motor deficits and degeneration of the nigrostriatal system. Increasing TGF-β signaling in the substantia nigra through adeno-associated virus expressing a constitutively active type I receptor significantly reduces 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurodegeneration and motor deficits. These results suggest that TGF-β signaling is critical for adult DA neuron survival and that modulating this signaling pathway has therapeutic potential in Parkinson disease.SIGNIFICANCE STATEMENT We show that reducing Transforming growth factor-β (TGF-β) signaling promotes Parkinson disease-related pathologies and motor deficits, and increasing TGF-β signaling reduces neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a parkinsonism-inducing agent. Our results provide a rationale to pursue a means of increasing TGF-β signaling as a potential therapy for Parkinson's disease.
Type: | Article |
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Title: | Deficiency in Neuronal TGF-β Signaling Leads to Nigrostriatal Degeneration and Activation of TGF-β Signaling Protects against MPTP Neurotoxicity in Mice |
Location: | United States |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1523/JNEUROSCI.2952-16.2017 |
Publisher version: | http://doi.org/10.1523/JNEUROSCI.2952-16.2017 |
Language: | English |
Additional information: | Copyright © 2017 the authors. This is an Open Access article published under a Creative Commons Attribution 4.0 International (CC BY 4.0) license (https://creativecommons.org/licenses/by/4.0/). |
Keywords: | AAV, MPTP, Parkinson's disease, TGF-β |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment |
URI: | https://discovery.ucl.ac.uk/id/eprint/1550475 |
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