Regulator of G protein signaling 6 (RGS6), a critical modulator of neurological function and disease

Neurological disorders encompass a wide variety of neurodegenerative and neuropsychiatric diseases and have severe debilitating and sometimes lethal effects on humans. Unfortunately, many current treatment options target disease symptomologies and fail to prevent or reverse disease progression, thus highlighting a critical need to identify the mechanisms underlying these disorders. G protein-coupled receptors (GPCRs) critically regulate neuronal communication processes and are highly druggable targets, accounting for over a third of currently marketed pharmaceuticals. However, there is a growing need for more specifically targeted therapeutics due to off-target effects. Regulator of G protein signaling (RGS) proteins negatively regulate GPCRs and represent an alternative to targeting GPCRs by allowing for greater spatial and temporal precision. RGS6 is an RGS protein that has been heavily implicated in numerous neurological disorders, including Alzheimer’s disease (AD), alcohol use disorders (AUDs), anxiety, depression, Parkinson’s disease (PD), and schizophrenia. Here, we sought to determine the role of RGS6 in these neurodegenerative and neurological disorders. Our findings reveal thatRGS6 plays a key role in neurons in the SNc, VTA, and hippocampus to prevent Parkinson’s-like neurodegeneration, promote alcohol drinking and relapse, and mediate exercise induced generation of new neurons and cognitive improvement in a mouse model of Alzheimer’s disease, respectively.