GUCY2C signaling limits dopaminergic neuron vulnerability to toxic insults.

ABSTRACT: Mitochondrial dysfunction and reactive oxygen species (ROS) accumulation within the substantia nigra pars compacta (SNpc) are central drivers of dopaminergic (DA) neuron death in Parkinson's disease (PD). Guanylyl cyclases and their second messenger cyclic (c)GMP support mitochondrial function, protecting against ROS and promoting cell survival in several tissues. However, the role of the guanylyl cyclase-cGMP axis in defining the vulnerability of DA neurons in the SNpc in PD remains unclear, in part due to the challenge of manipulating cGMP levels selectively in midbrain DA neurons. In that context, guanylyl cyclase C (GUCY2C), a receptor primarily expressed by intestinal epithelial cells, was discovered recently in midbrain DA neurons. Here, we demonstrate that GUCY2C promotes mitochondr

SUBMITTER: Cheslow L 

PROVIDER: S-EPMC11016112 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature