Antiseizure Medications in Pregnancy.

Epilepsy affects up to 15 million of people assigned female at birth of childbearing age globally. Up to 65% of these people with epilepsy and gestational capacity have an unplanned pregnancy. Seizure control during pregnancy is important for both the childbearer's and fetus' safety. There are multiple antiseizure medications (ASMs) that can be used to control epilepsy; however, each medication has its own teratogenic risk profile, which must be considered. The majority of these ASMs will require frequent plasma concentration monitoring during pregnancy with corresponding dosage adjustments. Dosages can be reduced back to prepregnancy levels within 3 weeks postpartum. Breastfeeding on ASMs is recommended.

Reversible Conformational Conversion of α-Synuclein into Toxic Assemblies by Glucosylceramide.

α-Synuclein (α-syn) aggregation is a key event in Parkinson's disease (PD). Mutations in glycosphingolipid (GSL)-degrading glucocerebrosidase are risk factors for PD, indicating that disrupted GSL clearance plays a key role in α-syn aggregation. However, the mechanisms of GSL-induced aggregation are not completely understood. We document the presence of physiological α-syn conformers in human midbrain dopamine neurons and tested their contribution to the aggregation process. Pathological α-syn assembly mainly occurred through the conversion of high molecular weight (HMW) physiological α-syn conformers into compact, assembly-state intermediates by glucosylceramide (GluCer), without apparent disassembly into free monomers. This process was reversible in vitro through GluCer depletion. Reducing GSLs in PD patient neurons with and without GBA1 mutations diminished pathology and restored physiological α-syn conformers that associated with synapses. Our work indicates that GSLs control the toxic conversion of physiological α-syn conformers in a reversible manner that is amenable to therapeutic intervention by GSL reducing agents.