The D2 Dopamine Receptor Interferes With the Protective Effect of the A_2A Adenosine Receptor on TDP-43 Mislocalization in Experimental Models of Motor Neuron Degeneration.

ABSTRACT: The A_2A adenosine receptor (A_2AR) and D2 dopamine receptor (D₂R) are two G-protein-coupled receptors that can form dimers and negatively regulate their partners. TAR DNA-binding protein (TDP-43) is a nuclear protein that has been implicated in amyotrophic lateral sclerosis (ALS). Mislocalization of TDP-43 from the nucleus to the cytoplasm is an early step of TDP-43 proteinopathy. Our previous studies indicated that A_2AR is a potential drug target for ALS because treatment with an A_2AR agonist (JMF1907; a T1-11 analog) prevents reactive oxygen species (ROS)-induced TDP-43 mislocalization in a motor neuron cell line (NSC34) and delays motor impairment in a TDP-43 transgenic ALS mouse model. Here, we set out to assess whether activation o

SUBMITTER: Lai CY 

PROVIDER: S-EPMC5869924 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature