Is activation of GDNF/RET signaling the answer for successful treatment of Parkinson's disease?A discussion of data from the culture dish to the clinic  

作　　者：James A.Conway Edgar R.Kramer 

机构地区：[1]Institute of Translational and Stratified Medicine,Peninsula Medical School,Faculty of Health,University of Plymouth,Devon,UK

出　　处：《Neural Regeneration Research》2022年第7期1462-1467,共6页中国神经再生研究（英文版）

基　　金：BRACE-Dementia Research,UK(ERK);Alzheimer’s Research UK;the Northcott Devon Medical Foundation(to JAC and ERK)for financial support。

摘　　要：The neurotrophic signaling of glial cell line-derived neurotrophic factor(GDNF)with its canonical receptor,the receptor tyrosine kinase RET,coupled together with the GDNF family receptor alpha 1 is important for dopaminergic neuron survival and physiology in cell culture experiments and animal models.This prompted the idea to try GDNF/RET signaling as a therapeutic approach to treat Parkinson’s disease with the hallmark of dopaminergic cell death in the substantia nigra of the midbrain.Despite several clinical trials with GDNF in Parkinson’s disease patients,which mainly focused on optimizing the GDNF delivery technique,benefits were only seen in a few patients.In general,the endpoints did not show significant improvements.This suggests that it will be helpful to learn more about the basic biology of this fascinating but complicated GDNF/RET signaling system in the dopaminergic midbrain and about recent developments in the field to facilitate its use in the clinic.Here we will refer to the latest publications and point out important open questions in the field.

关 键 词：Α-SYNUCLEIN clinical trials dopaminergic neurons glial cell line-derived neurotrophic factor GFRα1 gut-brain axis Nedd4 PARKIN Parkinson’s disease RET 

分 类 号：R742.5[医药卫生—神经病学与精神病学]