Disease models of anti-N-methyl-d-aspartate receptor encephalitis: Investigating pathogenesis and targeted therapy

Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a rare autoimmune disorder characterized by antibodies that specifically target the GluN1 subunit of NMDAR in neuronal cells. It is the most extensively studied form of autoimmune encephalitis (AE). Although it primarily affects young women, the condition can occur in individuals of all ages and genders. Our understanding of NMDAR encephalitis has advanced considerably since the identification of antibodies associated with this unique neuropsychiatric syndrome. Various cytokines, chemokines, and other molecules found in cerebrospinal fluid (CSF) have been investigated as potential triggers for the onset of NMDAR encephalitis. However, definitive biomarkers for disease development or prognosis remain elusive. The disorder generally responds well to immunotherapy, with many patients achieving favorable clinical outcomes. Nevertheless, diagnosing and managing NMDAR encephalitis remains challenging. Exploring the underlying pathophysiological mechanisms is crucial for improving diagnostic accuracy and treatment effectiveness. To this end, cellular and animal models of the disease are widely used to study its mechanisms, helping to control for confounding factors such as variable incidence rates and patient heterogeneity. Developing research models for anti-NMDAR encephalitis enables a deeper understanding of its pathogenic processes, providing valuable insights for precise clinical diagnosis and therapy. This review aims to clarify the pathogenic mechanisms and potential treatment strategies identified to date within the context of research models for anti-NMDAR encephalitis.