Progress in the mechanism of neuronal surface P antigen modulating hippocampal function and implications for autoimmune brain disease

Francisca Barake, Marcela Bravo-Zehnder, Alfonso González*

*Autor correspondiente de este trabajo

Producción científica: Contribución a una revistaArtículo de revisiónrevisión exhaustiva

1 Cita (Scopus)


Purpose of reviewThe aim of this study was to present a new regulation system in the hippocampus constituted by the neuronal surface P antigen (NSPA) and the tyrosine phosphatase PTPMEG/PTPN4, which provides mechanistic and therapeutic possibilities for cognitive dysfunction driven by antiribosomal P protein autoantibodies in patients with systemic lupus erythematosus (SLE).Recent findingsMice models lacking the function of NSPA as an E3 ubiquitin ligase show impaired glutamatergic synaptic plasticity, decreased levels of NMDAR at the postsynaptic density in hippocampus and memory deficits. The levels of PTPMEG/PTPN4 are increased due to lower ubiquitination and proteasomal degradation, resulting in dephosphorylation of tyrosines that control endocytosis in GluN2 NMDAR subunits. Adult hippocampal neurogenesis (AHN) that normally contributes to memory processes is also defective in the absence of NSPA.SummaryNSPA function is crucial in memory processes controlling the stability of NMDAR at PSD through the ubiquitination of PTPMEG/PTPN4 and also through AHN. As anti-P autoantibodies reproduce the impairments of glutamatergic transmission, plasticity and memory performance seen in the absence of NSPA, it might be expected to perturb the NSPA/PTPMEG/PTPN4 pathway leading to hypofunction of NMDAR. This neuropathogenic mechanism contrasts with that of anti-NMDAR antibodies also involved in lupus cognitive dysfunction. Testing this hypothesis might open new therapeutic possibilities for cognitive dysfunction in SLE patients bearing anti-P autoantibodies.

Idioma originalInglés
Páginas (desde-hasta)436-442
Número de páginas7
PublicaciónCurrent Opinion in Neurology
EstadoPublicada - 2022

Nota bibliográfica

Publisher Copyright:
© 2022 Lippincott Williams and Wilkins. All rights reserved.

Áreas temáticas de ASJC Scopus

  • Neurología
  • Neurología clínica


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