PT  - JOURNAL ARTICLE
AU  - Ina Tesseur
AU  - Andy Nguyen
AU  - Betty Chang
AU  - Lulin Li
AU  - Nathaniel S. Woodling
AU  - Tony Wyss-Coray
AU  - Jian Luo
TI  - Deficiency in Neuronal TGF-β Signaling Leads to Nigrostriatal Degeneration and Activation of TGF-β Signaling Protects against MPTP Neurotoxicity in Mice
AID  - 10.1523/JNEUROSCI.2952-16.2017
DP  - 2017 Apr 26
TA  - The Journal of Neuroscience
PG  - 4584--4592
VI  - 37
IP  - 17
4099  - http://www.jneurosci.org/content/37/17/4584.short
4100  - http://www.jneurosci.org/content/37/17/4584.full
SO  - J. Neurosci.2017 Apr 26; 37
AB  - 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.