The Emerging Role of Immunoglobulins and Complement in the Stimulation of Neuronal Activity and Repair: Not As Simple As We Thought

Overview

Journal Biomolecules

Publisher MDPI

Specialties Biochemistry
Molecular Biology

Date 2024 Oct 26

PMID 39456256

Authors

Tatyana Veremeyko

Natasha S Barteneva

Ivan Vorobyev

Eugene D Ponomarev

Affiliations

Soon will be listed here.

Abstract

Neurologic disorders such as traumatic brain injury, multiple sclerosis, Alzheimer's disease, and drug-resistant epilepsy have a high socioeconomic impact around the world. Current therapies for these disorders are often not effective. This creates a demand for the development of new therapeutic approaches to treat these disorders. Recent data suggest that autoreactive naturally occurring immunoglobulins produced by subsets of B cells, called B1 B cells, combined with complement, are actively involved in the processes of restoration of neuronal functions during pathological conditions and remyelination. The focus of this review is to discuss the possibility of creating specific therapeutic antibodies that can activate and fix complement to enhance neuronal survival and promote central nervous system repair after injuries associated with many types of neurodegenerative diseases.

References

Amara U, Flierl M, Rittirsch D, Klos A, Chen H, Acker B . Molecular intercommunication between the complement and coagulation systems. J Immunol. 2010; 185(9):5628-36. PMC: 3123139. DOI: 10.4049/jimmunol.0903678. View

Kim K, Wang X, Ragonnaud E, Bodogai M, Illouz T, DeLuca M . Therapeutic B-cell depletion reverses progression of Alzheimer's disease. Nat Commun. 2021; 12(1):2185. PMC: 8042032. DOI: 10.1038/s41467-021-22479-4. View

Xu X, Wittenberg N, Jordan L, Kumar S, Watzlawik J, Warrington A . A patterned recombinant human IgM guides neurite outgrowth of CNS neurons. Sci Rep. 2013; 3:2267. PMC: 3721078. DOI: 10.1038/srep02267. View

Sotnikov I, Veremeyko T, Starossom S, Barteneva N, Weiner H, Ponomarev E . Platelets recognize brain-specific glycolipid structures, respond to neurovascular damage and promote neuroinflammation. PLoS One. 2013; 8(3):e58979. PMC: 3608633. DOI: 10.1371/journal.pone.0058979. View

Schafer D, Lehrman E, Kautzman A, Koyama R, Mardinly A, Yamasaki R . Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron. 2012; 74(4):691-705. PMC: 3528177. DOI: 10.1016/j.neuron.2012.03.026. View

Schartz N, Aroor A, Li Y, Pinzon-Hoyos N, Brewster A . Mice deficient in complement C3 are protected against recognition memory deficits and astrogliosis induced by status epilepticus. Front Mol Neurosci. 2023; 16:1265944. PMC: 10682718. DOI: 10.3389/fnmol.2023.1265944. View

Carr K, Shah M, Garvin R, Shakir A, Jackson C . Post-Traumatic brain injury (TBI) presenting with Guillain-Barré syndrome and elevated anti-ganglioside antibodies: a case report and review of the literature. Int J Neurosci. 2014; 125(7):486-92. DOI: 10.3109/00207454.2014.957760. View

Vezzani A, Lang B, Aronica E . Immunity and Inflammation in Epilepsy. Cold Spring Harb Perspect Med. 2015; 6(2):a022699. PMC: 4743070. DOI: 10.1101/cshperspect.a022699. View

Chen C, Howie J, Ebrahimi M, Teymouri K, Woo J, Tiwari A . Analysis of the complement component C4 gene with schizophrenia subphenotypes. Schizophr Res. 2024; 271:309-318. DOI: 10.1016/j.schres.2024.07.039. View

10.

Michailidou I, Willems J, Kooi E, van Eden C, Gold S, Geurts J . Complement C1q-C3-associated synaptic changes in multiple sclerosis hippocampus. Ann Neurol. 2015; 77(6):1007-26. DOI: 10.1002/ana.24398. View

11.

Fokkink W, Selman M, Dortland J, Durmus B, Kuitwaard K, Huizinga R . IgG Fc N-glycosylation in Guillain-Barré syndrome treated with immunoglobulins. J Proteome Res. 2014; 13(3):1722-30. DOI: 10.1021/pr401213z. View

12.

Ghebrehiwet B, Randazzo B, Dunn J, Silverberg M, Kaplan A . Mechanisms of activation of the classical pathway of complement by Hageman factor fragment. J Clin Invest. 1983; 71(5):1450-6. PMC: 437009. DOI: 10.1172/jci110898. View

13.

McKee A, Daneshvar D . The neuropathology of traumatic brain injury. Handb Clin Neurol. 2015; 127:45-66. PMC: 4694720. DOI: 10.1016/B978-0-444-52892-6.00004-0. View

14.

Kopeikina E, Dukhinova M, Yung A, Veremeyko T, Kuznetsova I, Lau T . Platelets promote epileptic seizures by modulating brain serotonin level, enhancing neuronal electric activity, and contributing to neuroinflammation and oxidative stress. Prog Neurobiol. 2020; 188:101783. DOI: 10.1016/j.pneurobio.2020.101783. View

15.

Chen Y, Chu J, Chang R, Chun Wong G . The Complement System in the Central Nervous System: From Neurodevelopment to Neurodegeneration. Biomolecules. 2022; 12(2). PMC: 8869249. DOI: 10.3390/biom12020337. View

16.

Wen L, Yang X, Wu Z, Fu S, Zhan Y, Chen Z . The complement inhibitor CD59 is required for GABAergic synaptic transmission in the dentate gyrus. Cell Rep. 2023; 42(4):112349. DOI: 10.1016/j.celrep.2023.112349. View

17.

Kelso M, Gendelman H . Bridge between neuroimmunity and traumatic brain injury. Curr Pharm Des. 2013; 20(26):4284-98. PMC: 4135046. View

18.

Foley J, Conway E . Cross Talk Pathways Between Coagulation and Inflammation. Circ Res. 2016; 118(9):1392-408. DOI: 10.1161/CIRCRESAHA.116.306853. View

19.

Trebst C, Stangel M . Promotion of remyelination by immunoglobulins: implications for the treatment of multiple sclerosis. Curr Pharm Des. 2006; 12(2):241-9. DOI: 10.2174/138161206775193118. View

20.

Jarius S, Franciotta D, Bergamaschi R, Wildemann B, Wandinger K . Immunoglobulin M antibodies to aquaporin-4 in neuromyelitis optica and related disorders. Clin Chem Lab Med. 2010; 48(5):659-63. DOI: 10.1515/CCLM.2010.127. View