Novel bandlike signal abnormality suggestive of heterotopia in patient with a frameshift mutation.

Malformations of cortical development are associated with epilepsy and cognitive dysfunction, and can occur in patients with ion channel mutations. We report a novel and subtle bandlike subcortical heterotopia on integrated positron emission tomography-magnetic resonance imaging ( PET-MRI) in a patient with treatment-resistant epilepsy due to a de novo frameshift mutation. Our case highlights the potential for other channel mutations to cause both epilepsy and cortical malformations.

A Case of Recurrent Insomnia: Extending the Spectrum of Autoimmune Encephalitis.

Recurrent insomnia is an uncommon manifestation that is encountered rarely in a sleep clinic. We report a woman with recurrent insomnia due to an autoimmune process that resolved after a course of immunotherapy.

Novel immunological approaches for the treatment of Alzheimer's disease.

Alzheimer's disease (AD), the most prevalent form of dementia worldwide, can be deemed as the next global health epidemic. The biochemistry underlying deposition of amyloid beta (A β) and hyperphosphorylated tau aggregates in AD has been extensively studied. The oligomeric forms of A β that are derived from the normal soluble A β peptides are believed to be the most toxic.

GDE2 promotes neurogenesis by glycosylphosphatidylinositol-anchor cleavage of RECK.

The six-transmembrane protein glycerophosphodiester phosphodiesterase 2 (GDE2) induces spinal motor neuron differentiation by inhibiting Notch signaling in adjacent motor neuron progenitors. GDE2 function requires activity of its extracellular domain that shares homology with glycerophosphodiester phosphodiesterases (GDPDs). GDPDs metabolize glycerophosphodiesters into glycerol-3-phosphate and corresponding alcohols, but whether GDE2 inhibits Notch signaling by this mechanism is unclear.

GDE2 regulates subtype-specific motor neuron generation through inhibition of Notch signaling.

The specification of spinal interneuron and motor neuron identities initiates within progenitor cells, while motor neuron subtype diversification is regulated by hierarchical transcriptional programs implemented postmitotically. Here we find that mice lacking GDE2, a six-transmembrane protein that triggers motor neuron generation, exhibit selective losses of distinct motor neuron subtypes, specifically in defined subsets of limb-innervating motor pools that correlate with the loss of force-generating alpha motor neurons. Mechanistically, GDE2 is expressed by postmitotic motor neurons but utilizes extracellular glycerophosphodiester phosphodiesterase activity to induce motor neuron generation by inhibiting Notch signaling in neighboring motor neuron progenitors.

The antioxidant enzyme Prdx1 controls neuronal differentiation by thiol-redox-dependent activation of GDE2.

The six-transmembrane protein GDE2 controls the onset and progression of spinal motor neuron differentiation through extracellular glycerophosphodiester phosphodiesterase metabolism. Although this process is likely to be tightly regulated, the relevant mechanisms that modulate its activity are unknown. Here we show that the antioxidant scavenger peroxiredoxin1 (Prdx1) interacts with GDE2, and that loss of Prdx1 causes motor neuron deficits analogous to GDE2 ablation.