Repositioning of FDA-Approved antifungal agents to interrogate Acyl-CoA synthetase long chain family member 4 (ACSL4) in ferroptosis

Modeling ferroptosis in human dopaminergic neurons: Pitfalls and opportunities for neurodegeneration research

“…To address these limitations, a two-stage LUHMES differentiation protocol has been previously established [ [30] , [31] , [32] ], emphasizing factors such as cell number, differentiation periods, number of medium changes, and medium constituents. Strict adherence to this protocol has been shown to ensure interlaboratory consistency of experimental observations [ [37] , [38] , [39] , [40] ]. The two-step differentiation protocol halts proliferation of non-synchronized cells (days 0–2), enabling reproducible seeding of non-proliferating cells.…”

“…LUHMES cells exhibit autonomous pace-making activity and are consequently characterized by high metabolic turnover, contributing to their distinct responsiveness to the activation of ferroptosis [ 33 , 34 ]. The LUHMES model demonstrated stability in large-scale screenings [ 35 , 36 ] and a high degree of interlaboratory reproducibility [ [37] , [38] , [39] , [40] ]. Therefore, this cell model was chosen as an example of how to document and verify unique, experimentally quantifiable, molecular key events that allow an unequivocal determination of ferroptotic cell death.…”

The regulation and functions of ACSL3 and ACSL4 in the liver and hepatocellular carcinoma

“…38 Notwithstanding known issues with acquired resistance to apoptosis in liver cancer, 194 selective inhibition of ACSL4 could be a feasible approach for the targeted treatment of some HCC subtypes. The availability of newly identified small molecule inhibitors of ACSL4 195 including Abemaciclib as a candidate treatment for NASH, 49 and PRGL493 as a potential treatment for ACSL4expressing breast and prostate cancers, 196 opens up opportunities to investigate direct pharmacological inhibition of this enzyme in HCC.…”