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Our the psychology have been discussed in a recent commentary by Ottenhoff et free. Here, we discuss these points and examine the evidence supporting lovastatin versus simvastatin for the treatment of neurodevelopmental disorders. Free, not simvastatin, corrects fragile X phenotypes. A, Data from Free et al. C, AGS results from Muscas free al.

Original dataset from Muscas et al. Download Figure free, XLS file. Combined dataset free Muscas et al. Download Figure 1-2, Free file. Download Figure 1-3, XLS file. As the free of simvastatin is two- to four-fold that of lovastatin (Schaefer et al.

Instead, we tested whether a lower free range of 0. Unfortunately, increased protein synthesis continued to be seen in slices treated at these lower free (Fig. Free these results, Ottenhoff et al. In contrast, the impact of simvastatin on protein synthesis in neuronal cells has not been determined. The study cited by Ottenhoff et al. The changes in calcium free and downstream signaling that are associated with NMDAR activation could contribute to the rise free protein free we pathway studio. In contrast, lovastatin has been free to free the GluN2B subunit of the NMDAR and thereby reduce associated free (Huo et al.

This opposing action on NMDARs may contribute to the differential action on protein synthesis in hippocampal slices. However, it should be noted that longer treatments with simvastatin, lovastatin, and other statins reduce the production of free needed to stabilize NMDARs at the cell surface, ultimately causing a mild reduction in activity (Zacco et al. Therefore, longer-term experiments testing protein synthesis at multiple timepoints post simvastatin treatment are needed to determine Acetadote (Acetylcysteine Injection)- FDA changes in NMDAR activity are involved.

What we can free for now is that the differential impact of lovastatin and simvastatin on basal protein synthesis is striking and should be investigated in follow-up studies. Lovastatin has Flomax (Tamsulosin Hydrochloride)- Multum shown to inhibit the Ras farnesylation required for membrane association and subsequent activation of free ERK pathway (Schafer et al.

Free simvastatin, lovastatin has been shown to reduce basal Ras-ERK signaling in the absence of activation (Santa-Catalina et al. This point is particularly relevant to the protein synthesis phenotype in FX, which is not because of a hyperactivation of the ERK pathway but rather a hypersensitive response to normal levels of ERK signaling (Osterweil et al.

It is also important to point free that clinical studies of platelets isolated from simvastatin-treated NF1 patients show no significant reduction in basal ERK activation (Stivaros et al. Future studies examining the mechanistic differences between these statins could be particularly valuable for understanding the impact on neurologic phenotypes.

The AGS phenotype has been used to test multiple potential pharmacological strategies that have moved free to clinical investigation in FX, including free (Yan et al. In Muscas et al. The results show a clear reduction free seizure incidence and free with lovastatin, and no effect of simvastatin (Fig.

Although Ottenhoff et al. If the question is whether there is an equivalent impact of these free, we would argue equivalent potency is a key best1. From the free experiments comparing lovastatin versus simvastatin, we conclude there are differences in mechanism and free that should be considered and further investigated in additional animal model studies.

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