| First Author | Tesseur I | Year | 2017 |
| Journal | J Neurosci | Volume | 37 |
| Issue | 17 | Pages | 4584-4592 |
| PubMed ID | 28363982 | Mgi Jnum | J:241353 |
| Mgi Id | MGI:5901950 | Doi | 10.1523/JNEUROSCI.2952-16.2017 |
| Citation | Tesseur I, et al. (2017) Deficiency in Neuronal TGF-beta Signaling Leads to Nigrostriatal Degeneration and Activation of TGF-beta Signaling Protects against MPTP Neurotoxicity in Mice. J Neurosci 37(17):4584-4592 |
| abstractText | Transforming growth factor-beta (TGF-beta) plays an important role in the development and maintenance of embryonic dopaminergic (DA) neurons in the midbrain. To study the function of TGF-beta signaling in the adult nigrostriatal system, we generated transgenic mice with reduced TGF-beta signaling in mature neurons. These mice display age-related motor deficits and degeneration of the nigrostriatal system. Increasing TGF-beta 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-beta 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-beta (TGF-beta) signaling promotes Parkinson disease-related pathologies and motor deficits, and increasing TGF-beta 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-beta signaling as a potential therapy for Parkinson's disease. |
