The role of D1 dopamine receptors and phospho-ERK in mediating cytotoxicity. Commentary.

Striatal neurodegeneration observed in several neurological diseases, occurs through unknown mechanisms. Recent evidence suggests that its pathogenesis may be linked, in part, to high synaptic levels of dopamine (DA), which can then cause neurotoxicity of striatal neurons through mitogen-activated protein kinases (MAPKs). Here we comment on the role of extracellular signal-regulated kinase (ERK) activation in the cytotoxicity mediated upon activation of the D1 DA receptor, and describe a possible mechanism for phospho-ERK (p-ERK) in inducing cytotoxicity.