AUTHOR=Moehle Mark S. 

TITLE=Mechanisms of GNAL linked dystonia

JOURNAL=Dystonia

VOLUME=3

YEAR=2024

URL=https://www.frontierspartnerships.org/journals/dystonia/articles/10.3389/dyst.2024.12079

DOI=10.3389/dyst.2024.12079

ISSN=2813-2106

ABSTRACT=<p>Mutations in the <italic>GNAL</italic> gene, encoding Gα<sub>olf</sub>, are causative for an adult-onset, isolated dystonia that may provide unique insights into the etiology of adult-onset idiopathic dystonia. Gα<sub>olf</sub> is an alpha subunit of heterotrimeric G protein that replaces Gα<sub>s</sub> in the striatum and has unique expression patterns outside of the striatum. Gα<sub>olf</sub> 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<sub>olf</sub> function, and how this is corrupted by <italic>GNAL</italic> mutations to cause dystonia. Thes include the molecular signaling and expression profiles of Gα<sub>olf</sub> and the other G proteins, β<sub>2</sub>γ<sub>7</sub>, complexedwith it., Additionally, we will discuss the circuits that Gα<sub>olf</sub> influences, and how <italic>GNAL</italic> mutations may reorganize these circuits to cause dystonia.</p>