A5014067858- Genetics and Neurodevelopmental Disorders
- Neuroscience and Neuropharmacology Research
- Cellular transport and secretion
- Receptor Mechanisms and Signaling
- Ion channel regulation and function
- Nitric Oxide and Endothelin Effects
- Genetic Neurodegenerative Diseases
Johns Hopkins University
2017-2020
Johns Hopkins Medicine
2017
Children's Hospital of Philadelphia
2017
University of Pennsylvania
2017
ATAD1 encodes Thorase, a mediator of α-amino-3-hydroxy-5-methylisoxazole-4-proprionate (AMPA) receptor recycling; in this work, we characterized the phenotype resulting from mutations and developed targeted therapy both mice humans.Using exome sequencing, identified novel mutation (p.E276X) as etiology devastating neurologic disorder by hypertonia, seizures, death consanguineous family. We postulated that pathogenesis was result excessive AMPA activity designed therapeutic approach using...
The AAA+ adenosine triphosphatase (ATPase) Thorase plays a critical role in controlling synaptic plasticity by regulating the expression of surface α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Bidirectional sequencing exons ATAD1, gene encoding Thorase, cohort patients with schizophrenia and healthy controls revealed rare variants. These variants caused defects glutamatergic signaling impairing AMPAR internalization recycling mouse primary cortical neurons. This...
The regulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) trafficking affects multiple brain functions, such as learning and memory. We have previously shown that Thorase plays an important role in the internalization AMPARs from synaptic membrane. Here, we show N-methyl-d-aspartate (NMDAR) activation leads to increased S-nitrosylation N-ethylmaleimide-sensitive factor (NSF). stabilizes Thorase-AMPAR complexes enhances AMPAR interaction with protein-interacting...