Complement in neurological disorders and emerging complement-targeted therapeutics.
Animals
Complement Inactivating Agents
/ administration & dosage
Complement Inactivator Proteins
/ administration & dosage
Complement System Proteins
/ immunology
Drug Delivery Systems
/ methods
Humans
Immunoglobulins, Intravenous
/ administration & dosage
Immunotherapy
/ methods
Nervous System Diseases
/ immunology
Signal Transduction
/ drug effects
Synapses
/ drug effects
Journal
Nature reviews. Neurology
ISSN: 1759-4766
Titre abrégé: Nat Rev Neurol
Pays: England
ID NLM: 101500072
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
accepted:
07
08
2020
pubmed:
3
10
2020
medline:
18
1
2022
entrez:
2
10
2020
Statut:
ppublish
Résumé
The complement system consists of a network of plasma and membrane proteins that modulate tissue homeostasis and contribute to immune surveillance by interacting with the innate and adaptive immune systems. Dysregulation, impairment or inadvertent activation of complement components contribute to the pathogenesis of some autoimmune neurological disorders and could even contribute to neurodegenerative diseases. In this Review, we summarize current knowledge about the main functions of the complement pathways and the involvement of complement in neurological disorders. We describe the complex network of complement proteins that target muscle, the neuromuscular junction, peripheral nerves, the spinal cord or the brain and discuss the autoimmune mechanisms of complement-mediated myopathies, myasthenia, peripheral neuropathies, neuromyelitis and other CNS disorders. We also consider the emerging role of complement in some neurodegenerative diseases, such as Alzheimer disease, amyotrophic lateral sclerosis and even schizophrenia. Finally, we provide an overview of the latest complement-targeted immunotherapies including monoclonal antibodies, fusion proteins and peptidomimetics that have been approved, that are undergoing phase I-III clinical trials or that show promise for the treatment of neurological conditions that respond poorly to existing immunotherapies.
Identifiants
pubmed: 33005040
doi: 10.1038/s41582-020-0400-0
pii: 10.1038/s41582-020-0400-0
pmc: PMC7528717
doi:
Substances chimiques
Complement Inactivating Agents
0
Complement Inactivator Proteins
0
Immunoglobulins, Intravenous
0
Complement System Proteins
9007-36-7
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
601-617Références
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