Epac as a tractable therapeutic target

Slika, Hasan; Mansour, Hadi; Nasser, Suzanne A.; Shaito, Abdullah; Kobeissy, Firas; Orekhov, Alexander N.; Pintus, Gianfranco; Eid, Ali H.

doi:10.1016/j.ejphar.2023.175645

Cited by 6 publications

(1 citation statement)

References 162 publications

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“…Similarly, increasing cAMP through inhibiting its metabolism through phosphodiesterase may provide therapeutic efficacy, but may not allow for precise control of cAMP production in response to upstream neurotransmitter signaling [56]. Targeting of downstream effectors of cAMP produced by Gα olf such as downstream targets of protein kinase A and cyclic nucleotide gated channels also possible [57,58], but further understanding of how these targets are altered in pre-clinical models of GNAL dystonia will be necessary.…”

Section: Targeting Gα Olf For Therapeutic Benefitmentioning

confidence: 99%

Mechanisms of GNAL linked dystonia

Moehle

2024

Dystonia

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Mutations in the GNAL gene, encoding Gαolf, are causative for an adult-onset, isolated dystonia that may provide unique insights into the etiology of adult-onset idiopathic dystonia. Gαolf is an alpha subunit of heterotrimeric G protein that replaces Gαs in the striatum and has unique expression patterns outside of the striatum. Gαolf 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 Gαolf function, and how this is corrupted by GNAL mutations to cause dystonia. Thes include the molecular signaling and expression profiles of Gαolf and the other G proteins, β2γ7, complexedwith it., Additionally, we will discuss the circuits that Gαolf influences, and how GNAL mutations may reorganize these circuits to cause dystonia.

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Section: Targeting Gα Olf For Therapeutic Benefitmentioning

confidence: 99%