Publications by authors named "Molly E Muehlebach"
The unfolded protein response pathway is an evolutionarily conserved cytoprotective signaling cascade, essential for cell function and survival. Unfolded protein response signaling is tightly integrated with bone cell differentiation and function, and chronic unfolded protein response activation has been identified in bone disease. The unfolded protein response has been found to promote oncogenesis and drug resistance, raising the possibility that unfolded protein response modulators may have activity as anti-cancer agents.
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- Nitrogen bisphosphonates like zoledronic acid treat osteolytic bone diseases by targeting farnesyl diphosphate synthase (FDPS), but their strong bone affinity limits their systemic use.
- RAM2061, a novel GGDPS inhibitor, shows promising drug-like qualities, such as prolonged half-life and anti-cancer effects in mouse models, and impacts osteoclast biology by disrupting differentiation and function.
- Although RAM2061 treatment didn't significantly affect overall bone turnover in mice, it reduced mature osteoclast numbers, signaling its potential for further investigation in bone remodeling therapies.
Geranylgeranyl diphosphate synthase (GGDPS), an enzyme in the isoprenoid biosynthesis pathway, is responsible for the production of geranylgeranyl pyrophosphate (GGPP). GGPP serves as a substrate for the post-translational modification (geranylgeranylation) of proteins, including those belonging to the Ras superfamily of small GTPases. These proteins play key roles in signalling pathways, cytoskeletal regulation and intracellular transport, and in the absence of the prenylation modification, cannot properly localise and function.
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