J.B.H. Wilke, H. Ehrenreich, and M. Hollmann (2019).
Autoantibodies against NMDA receptors – Janus-faced molecules?
Neuroforum 25(2).
doi: 10.1515/nf-2018-0025
Just like the two-faced Roman god of the beginning and the end, Janus, autoantibodies against N-methyl-D-aspartate receptors (NMDAR) have dualistic effects on the human brain. In recent years, autoantibodies against the GluN1 subunit of NMDAR gained attention by physicians world-wide as a diagnostic criterion for the so-called anti-NMDAR encephalitis. Seemingly contradictory was the subsequent identification of GluN1 autoantibodies (GluN1-AB) in healthy subjects. By now, many studies analysed the abundance of GluN1-AB, their immunoglobulin classes, epitopes, and mode of action. Interestingly, GluN1-AB exert their effects by cross-linking NMDAR, which triggers their internalisation. In this review we will discuss how the resulting decrease of surface NMDAR has the potential to protect neurons from neurotoxic events during states of hyperexcitation while at the same time inducing psychosis-like symptoms upon access to the brain. Additionally, we will discuss the pathogenicity of GluN1-AB in the context of brain inflammation.