Rescuing the phenotype of STXBP1 encephalopathy: Therapeutic potential of positive allosteric modulators targeting glutamate receptors
Carlos Gomez Martinez, Altair Brito Dos Santos, Joakim Palmqvist, Silas Dalum Larsen, Victor Larsen, Sarah Elisabeth Andersen, Anne Marie Nordvig Petersen, Jakob Balslev Sørense, Robertas Guzulaitis, Jean-François Perrier · FENS Forum 2024
De novo mutations in STXBP1 are among the most prevalent causes of neurodevelopmental disorders, leading to haploinsufficiency, cortical hyperexcitability, epilepsy, and motor impairments. STXBP1 encodes for Munc18-1, an essential protein for synaptic transmission. In a mouse model of the disease, we found that excitatory synapses, not inhibitory synapses, are impaired during early stages of the disease. Consequently, excitatory synapses fail to recruit parvalbumin-positive (PV) inhibitory interneurons in feedforward inhibitory microcircuits, leading to cortical hyperexcitability. In this stud
ePoster · Neuroscience