Award
National Institute of Neurological Disorders and Stroke 1F31NS139574-01A1
Evaluating the protein homeostasis of N-methyl-D-aspartate receptors containing pathogenic GluN2B subunits
Recipient
CASE WESTERN RESERVE UNIVERSITY
Award Amount
$42,780.00
Ceiling
$42,780.00
Awarded
June 30, 2025
Identifier
1F31NS139574-01A1
Research project to study the protein homeostasis of NMDA receptors with pathogenic GluN2B subunits to understand molecular mechanisms and identify therapeutic targets for neurological disorders.
Description
This project aims to elucidate the proteostasis network regulating NMDA receptor folding, assembly, trafficking, and degradation, focusing on disease-associated variants (DAVs) within the GluN2B subunit. The study will investigate how DAVs impair receptor assembly, activate ER quality control checkpoints, and are degraded via autophagy pathways, including lysosomal degradation and ER-phagy. The research will utilize biochemical and molecular techniques, including studies on cortical neurons derived from human induced pluripotent stem cells, to identify novel therapeutic targets for disorders involving NMDAR dysregulation such as GRIN diseases, schizophrenia, autism spectrum disorder, and Alzheimer’s disease.