Clinical and biochemical evaluation of rituximab as add on therapy in neuromyelitis optica spectrum disorders.

OBJECTIVE: This study assesses the efficacy of rituximab in the treatment of neuromyelitis optica spectrum disorders (NMOSD). METHODS: The study initially included 40 patients with NMOSD diagnosed, after excluding patients who did not meet the complete inclusion criteria. Patients in the conventional group received routine clinical treatment, while patients in the study group received additional treatment with rituximab on the basis of the conventional treatment. Baseline data and clinically relevant indicators were collected for all patients, and the efficacy was compared between the two groups. RESULTS: Baseline data were comparable between the two groups (p > 0.05). The EDSS scores after clinical treatment in the study group were lower than those in the conventional group, and the difference in EDSS scores before and after treatment was higher than that in the conventional group (p < 0.05). The difference in visual acuity correction before and after treatment was not significant between the two groups (p > 0.05). Laboratory indicators in the study group after clinical treatment were superior to those in the conventional group (all p < 0.05). The recurrence rate after clinical treatment in the study group was significantly lower than that in the conventional group (p < 0.05). Adverse reactions after clinical treatment in the study group were less than those in the conventional group (p < 0.05). CONCLUSION: This study found that rituximab demonstrated significant efficacy in the acute attacks and recurrence prevention of NMOSD, emphasizing its relatively good safety and tolerability. It highlights the potential of rituximab in treating NMOSD and provides valuable insights for future disease management.

Estrogen receptor α promotes Cav1.2 ubiquitination and degradation in neuronal cells and in APP/PS1 mice.

Cav1.2 is the pore-forming subunit of L-type voltage-gated calcium channel (LTCC) that plays an important role in calcium overload and cell death in Alzheimer's disease. LTCC activity can be regulated by estrogen, a sex steroid hormone that is neuroprotective. Here, we investigated the potential mechanisms in estrogen-mediated regulation of Cav1.2 protein. We found that in cultured primary neurons, 17ß-estradiol (E2) reduced Cav1.2 protein through estrogen receptor α (ERα). This effect was offset by a proteasomal inhibitor MG132, indicating that ubiquitin-proteasome system was involved. Consistently, the ubiquitin (UB) mutant at lysine 29 (K29R) or the K29-deubiquitinating enzyme TRAF-binding protein domain (TRABID) attenuated the effect of ERα on Cav1.2. We further identified that the E3 ligase Mdm2 (double minute 2 protein) and the PEST sequence in Cav1.2 protein played a role, as Mdm2 overexpression and the membrane-permeable PEST peptides prevented ERα-mediated Cav1.2 reduction, and Mdm2 overexpression led to the reduced Cav1.2 protein and the increased colocalization of Cav1.2 with ubiquitin in cortical neurons in vivo. In ovariectomized (OVX) APP/PS1 mice, administration of ERα agonist PPT reduced cerebral Cav1.2 protein, increased Cav1.2 ubiquitination, and improved cognitive performances. Taken together, ERα-induced Cav1.2 degradation involved K29-linked UB chains and the E3 ligase Mdm2, which might play a role in cognitive improvement in OVX APP/PS1 mice.