Anti-NMDA and Anti-AMPA Receptor Antibodies in Central Disorders: Preclinical Approaches to Assess Their Pathological Role and Translatability to Clinic

Abstract

Autoantibodies against NMDA and AMPA receptors have been identified in the central nervous system of patients suffering from brain disorders characterized by neurological and psychiatric symptoms. It has been demonstrated that these autoantibodies can affect the functions and/or the expression of the targeted receptors, altering synaptic communication. The importance to clarify, in preclinical models, the molecular mechanisms involved in the autoantibody-mediated effects has emerged in order to understand their pathogenic role in central disorders, but also to propose new therapeutic approaches for preventing the deleterious central consequences. In this review, we describe some of the available preclinical literature concerning the impact of antibodies recognizing NMDA and AMPA receptors in neurons. This review discusses the cellular events that would support the detrimental roles of the autoantibodies, also illustrating some contrasting findings that in our opinion deserve attention and further investigations before translating the preclinical observations to clinic.

Basic, Translational, and Clinical Research on Dementia

“…The results obtained with the anti-GluA autoantibodies are highly heterogenous and more investigations are needed to clarify their role in dictating the changes in AMPA receptor expression and functions. On the contrary, the results concerned with anti-GluN antibodies are consistent with an antibody-induced internalization of the NMDA receptor subunit that well accounts for the synaptic desynchronization that supports some of the clinical manifestations observed in patients [14].…”

“…Their impact on the functions and/or the expression of the targeted receptors can alter synaptic communication. Olivero et al [14] have attempted to clarify the molecular mechanisms involved in the autoantibody-mediated effects in preclinical models, in order to understand their pathogenic role in central disorders, but also to propose new therapeutic approaches for preventing the deleterious central consequences. NMDA receptors are tetramerically assembled, including the obligatory GluN1 subunits associated with the GluN2 (A-D) and/or the GluN3 (A-B) subunits [15].…”