N-cadherin is a Novel ERα Anchor that Protects Against 6-OHDA Damage to Dopaminergic Cells

Abstract

Parkinson's disease is a neurodegenerative disorder caused by the selective loss of dopaminergic (DA) neurons. In this study, we investigated the protective roles of glial cell line-derived neurotrophic factor (GDNF) and 17β-estradiol (E2) in the neuron cell line MN9D following treatment with 6-hydroxydopamine. This result showed that phosphorylation of protein kinase B (Akt) was significantly increased in treated MN9D cells following co-application of GDNF and E2 compared with only GDNF or E2. Moreover, GDNF enhanced the E2-induced translocation of estrogen receptor α (ERα) from the cytosol to the membrane. Immunoprecipitation experiments showed that the translocated ERα interacted with neural cadherin (N-cadherin) in the membrane. Site-directed mutagenesis of Tyr860 (Y860) in N-cadherin inhibited its interaction with ERα. Combined with the fact that GDNF can stimulate N-cadherin Y860 phosphorylation, we hypothesize that N-cadherin is a novel anchor for ERα, and phosphorylation at Y860 further increases ER's capacity to activate the neuroprotective phosphatidyl inositol-3 kinase/Akt pathway. This study provides evidence that co-application of GDNF and E2 exert important protective effects on DA neurons by increasing the interaction between ERα and N-cadherin.

Identification of cerebrospinal fluid biomarkers for parkinsonism using a proteomics approach

“…The adhesion protein Cadherin 2 may play a protective role in dopaminergic neurons 20 – 22 . Loss of Cadherin-2 compromises neuronal differentiation, via the Wnt signalling pathway 23 .…”

Purple sweet potato delphinidin-3-rutin represses glioma proliferation by inducing miR-20b-5p/Atg7-dependent cytostatic autophagy

“…Data were presented as means ± SD from three independent immunoblotting assays. 58 Phosphorylated and total protein levels were determined and quantified by three successive immunoblotting experiments.…”