Correction to: Ret is essential to mediate GDNF’s neuroprotective and neuroregenerative effect in a Parkinson disease mouse model

Correction to: Cell Death Dis. (2016) 7, e2359; https://doi.org/10.1038/cddis.2016.263; published online 08 September 2016</jats:p

Channeled polymeric scaffolds with polypeptide gel filling for lengthwise guidance of neural cells

CNS damages are often irreversible since neurons of the central nervous system are unable to regenerate after an injury. As a new strategy within the nervous system tissue engineering, multifunctional systems based on two different biomaterials to support axonal guidance in damaged connective tracts have been developed herein. These systems are composed of a channeled scaffold made of ethyl acrylate and hydroxyethyl acrylate copolymer, P(EA-co-HEA), with parallel tubular micropores, combined with an injectable and in situ gelable self-assembling polypeptide (RAD16-I) as pores filler. The polymer scaffold is intended to provide a three-dimensional context for axon growth; subsequently, its morphology and physicochemical parameters have been determined by scanning electron microscopy, density measurements and compression tests. Besides, the hydrogel acts as a cell-friendly nanoenvironment while it creates a gradient of bioactive molecules (nerve growth factor, NGF) along the scaffolds channels; the chemotactic effect of NGF has been evaluated by a quantitative ELISA assay. These multifunctional systems have shown ability to keep circulating NGF, as well as proper short-term in vitro biological response with glial cells and neural progenitors.The authors acknowledge funding through the Spanish Ministerio de Ciencia e Innovacion (MAT2011-28791-C03-02 and -03). Dr. J.M. Garcia Verdugo (Department of Comparative Neurobiology, Cavanilles Institute of Biodiversity and Evolutive Biology, Universitat de Valencia) is thanked for kindly providing the cells employed in this work.Conejero García, Á.; Vilarino-Feltrer, G.; Martínez Ramos, C.; Monleón Pradas, M.; Vallés Lluch, A. (2015). Channeled polymeric scaffolds with polypeptide gel filling for lengthwise guidance of neural cells. European Polymer Journal. 70:331-341. doi:10.1016/j.eurpolymj.2015.07.033S3313417

Ret is essential to mediate GDNF’s neuroprotective and neuroregenerative effect in a Parkinson disease mouse model

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