Mechanisms of GNAL linked dystonia

Mutations in the GNAL gene, encoding Gα olf , are causative for an adult-onset, isolated dystonia that may provide unique insights into the etiology of adult-onset idiopathic dystonia. Gα olf is an alpha subunit of heterotrimeric G protein that replaces Gα s in the striatum and has unique expression patterns outside of the striatum. Gα olf additionally has defined molecular functions in GPCR signaling. These defined molecular pathways and expression pathways point to defined circuit deficits underlying the causes of this adult-onset dystonia that may provide additional insights into broader idiopathic dystonia. Here, we will review the available evidence for normal Gα olf function, and how this is corrupted by GNAL mutations to cause dystonia. Thes include the molecular signaling and expression profiles of Gα olf and the other G proteins, β 2 γ 7 , complexedwith it., Additionally, we will discuss the circuits that Gα olf influences, and how GNAL mutations may reorganize these circuits to cause dystonia.