Chemogenetics for cell-type-specific modulation of signalling and neuronal activity

Kang, Hye Jin; Minamimoto, Takafumi; Wess, Jürgen; Roth, Bryan L.

doi:10.1038/s43586-023-00276-1

Cited by 5 publications

(1 citation statement)

References 137 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, the authors presented the first two Gα12-specific DREADDs (designer receptors exclusively activated by designer drugs), engineered receptors that respond to a synthetic ligand. Previously, DREADDs were only available as the Gαs, Gαi/o, and Gαq/11-coupled M3Ds, M4Di, and M3Dq GPCRs [109]. Therefore, this TGF-α shedding assay has extended the availability of DREADDs to all four Gα protein subfamilies.…”

Section: Tgf-α Shedding Assaymentioning

confidence: 99%

Exploiting Cell-Based Assays to Accelerate Drug Development for G Protein-Coupled Receptors

Wu,

Jensen,

Rossner

et al. 2024

IJMS

View full text Add to dashboard Cite

G protein-coupled receptors (GPCRs) are relevant targets for health and disease as they regulate various aspects of metabolism, proliferation, differentiation, and immune pathways. They are implicated in several disease areas, including cancer, diabetes, cardiovascular diseases, and mental disorders. It is worth noting that about a third of all marketed drugs target GPCRs, making them prime pharmacological targets for drug discovery. Numerous functional assays have been developed to assess GPCR activity and GPCR signaling in living cells. Here, we review the current literature of genetically encoded cell-based assays to measure GPCR activation and downstream signaling at different hierarchical levels of signaling, from the receptor to transcription, via transducers, effectors, and second messengers. Singleplex assay formats provide one data point per experimental condition. Typical examples are bioluminescence resonance energy transfer (BRET) assays and protease cleavage assays (e.g., Tango or split TEV). By contrast, multiplex assay formats allow for the parallel measurement of multiple receptors and pathways and typically use molecular barcodes as transcriptional reporters in barcoded assays. This enables the efficient identification of desired on-target and on-pathway effects as well as detrimental off-target and off-pathway effects. Multiplex assays are anticipated to accelerate drug discovery for GPCRs as they provide a comprehensive and broad identification of compound effects.

show abstract

Section: Tgf-α Shedding Assaymentioning

confidence: 99%