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

Abstract

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.

Emerging Materials, Wearables, and Diagnostic Advancements in Therapeutic Treatment of Brain Diseases

“…Each autoimmune illness is caused by a unique set of genes that have not yet been identified, but several experimental techniques, including genome-wide correlation scans, have been employed to pinpoint specific genetic risk variations that might or may not be at fault [ 54 , 55 , 56 ]. Researchers are now increasingly understanding the genesis of autoimmune disorders including Type 1 diabetes and rheumatoid arthritis thanks to work on genomic sequencing and hereditary trait transmission studies [ 49 , 56 , 57 , 58 ]. As the brain is a complicated organ, studying the impact of genetic changes on ABD poses a number of challenges, not the least of which is the fact that the exact cause of ABD is mostly unclear.…”

“…The decreased functionality of the brain brought on by this inflammation may result in psychological problems [ 63 , 64 ]. The wide range of ailments makes diagnosis difficult and frequently delayed for the brain related diseases [ 54 , 57 , 59 , 65 ].…”

“…The survival is often significantly better, and the cancer correlations can vary. It is believed that the autoantibodies that cause these illnesses are primarily pathogenic and have temporary effects on synaptic function in nerves with minimal loss of dopaminergic neurons [ 54 , 57 , 77 , 78 ].…”

“…These include exhilaration, fear, violence, increased anxiety, obsessive behaviours, delusion, and abnormal sexual conduct [ 49 , 75 , 80 ]. Anti–α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (Anti-AMPAR) receptor and anti-gamma aminobutyric acid-B (Anti-GABA) receptor both have the potential to produce strong early mental signs, although Anti-N-methyl D-aspartate (Anti-NMDAR) receptor encephalitis is widely known for having higher symptoms [ 57 , 81 , 82 ]. Overall, anti-NMDAR encephalitis is more frequent and should be suspected initially; this is true for young adults and children, though they can both induce similar appearances in people of all ages.…”