RT Journal Article
T1 Development and characterization of functional antibodies targeting NMDA receptors
A1 Tajima, Nami
A1 Simorowski, Noriko
A1 Yovanno, Remy A.
A1 Regan, Michael C.
A1 Michalski, Kevin
A1 Gómez García, Ricardo
A1 Lau, Albert Y.
A1 Furukawa, Hiro
AB N-methyl-D-aspartate receptors (NMDARs) are critically involved in basic brain functions and neurodegeneration as well as tumor invasiveness. Targeting specific subtypes of NMDARs with distinct activities has been considered an effective therapeutic strategy for neurological disorders and diseases. However, complete elimination of off-target effects of small chemical compounds has been challenging and thus, there is a need to explore alternative strategies for targeting NMDAR subtypes. Here we report identification of a functional antibody that specifically targets the GluN1-GluN2B NMDAR subtype and allosterically down-regulates ion channel activity as assessed by electrophysiology. Through biochemical analysis, x-ray crystallography, single-particle electron cryomicroscopy, and molecular dynamics simulations, we show that this inhibitory antibody recognizes the amino terminal domain of the GluN2B subunit and increases the population of the non-active conformational state. The current study demonstrates that antibodies may serve as specific reagents to regulate NMDAR functions for basic research and therapeutic objectives.
PB Nature Research
YR 2022
FD 2022-02-17
LK https://hdl.handle.net/20.500.14352/91783
UL https://hdl.handle.net/20.500.14352/91783
LA eng
NO Tajima, N., Simorowski, N., Yovanno, R.A. et al. Development and characterization of functional antibodies targeting NMDA receptors. Nat Commun 13, 923 (2022). https://doi.org/10.1038/s41467-022-28559-3
DS Docta Complutense
RD 12 abr 2025