Ret is essential to mediate GDNF's neuroprotective and neuroregenerative effect in a Parkinson disease mouse model
Standard
Ret is essential to mediate GDNF's neuroprotective and neuroregenerative effect in a Parkinson disease mouse model. / Drinkut, Anja; Tillack, Karsten; Meka, Praveen; Schulz, Jorg B; Kügler, Sebastian; Kramer, Edgar R.
In: CELL DEATH DIS, Vol. 7, No. 9, 08.09.2016, p. e2359.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Ret is essential to mediate GDNF's neuroprotective and neuroregenerative effect in a Parkinson disease mouse model
AU - Drinkut, Anja
AU - Tillack, Karsten
AU - Meka, Praveen
AU - Schulz, Jorg B
AU - Kügler, Sebastian
AU - Kramer, Edgar R
PY - 2016/9/8
Y1 - 2016/9/8
N2 - Glial cell line-derived neurotrophic factor (GDNF) is a potent survival and regeneration-promoting factor for dopaminergic neurons in cell and animal models of Parkinson disease (PD). GDNF is currently tested in clinical trials on PD patients with so far inconclusive results. The receptor tyrosine kinase Ret is the canonical GDNF receptor, but several alternative GDNF receptors have been proposed, raising the question of which signaling receptor mediates here the beneficial GDNF effects. To address this question we overexpressed GDNF in the striatum of mice deficient for Ret in dopaminergic neurons and subsequently challenged these mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Strikingly, in this established PD mouse model, the absence of Ret completely abolished GDNF's neuroprotective and regenerative effect on the midbrain dopaminergic system. This establishes Ret signaling as absolutely required for GDNF's effects to prevent and compensate dopaminergic system degeneration and suggests Ret activation as the primary target of GDNF therapy in PD.
AB - Glial cell line-derived neurotrophic factor (GDNF) is a potent survival and regeneration-promoting factor for dopaminergic neurons in cell and animal models of Parkinson disease (PD). GDNF is currently tested in clinical trials on PD patients with so far inconclusive results. The receptor tyrosine kinase Ret is the canonical GDNF receptor, but several alternative GDNF receptors have been proposed, raising the question of which signaling receptor mediates here the beneficial GDNF effects. To address this question we overexpressed GDNF in the striatum of mice deficient for Ret in dopaminergic neurons and subsequently challenged these mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Strikingly, in this established PD mouse model, the absence of Ret completely abolished GDNF's neuroprotective and regenerative effect on the midbrain dopaminergic system. This establishes Ret signaling as absolutely required for GDNF's effects to prevent and compensate dopaminergic system degeneration and suggests Ret activation as the primary target of GDNF therapy in PD.
KW - Journal Article
U2 - 10.1038/cddis.2016.263
DO - 10.1038/cddis.2016.263
M3 - SCORING: Journal article
C2 - 27607574
VL - 7
SP - e2359
JO - CELL DEATH DIS
JF - CELL DEATH DIS
SN - 2041-4889
IS - 9
ER -