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PMID: 12043837 Published · ppublish English Journal Article Review

Harnessing the immune system for neuroprotection: therapeutic vaccines for acute and chronic neurodegenerative disorders.

Cellular and molecular neurobiology ·Vol. 21 ·No. 6 ·2001-12-00 ·Pages 617-27

Schwartz M

Abstract

Nerve injury causes degeneration of directly injured neurons and the damage spreads to neighboring neurons. Research on containing the damage has been mainly pharmacological, and has not recruited the immune system. We recently discovered that after traumatic injury to the central nervous system (spinal cord or optic nerve), the immune system apparently recognizes certain injury-associated self-compounds as potentially destructive and comes to the rescue with a protective antiself response mediated by a T-cell subpopulation that can recognize self-antigens. We further showed that individuals differ in their ability to manifest this protective autoimmunity, which is correlated with their ability to resist the development of autoimmune diseases. This finding led us to suggest that the antiself response must be tightly regulated to be expressed in a beneficial rather than a destructive way. In seeking to develop a neuroprotective therapy by boosting the beneficial autoimmune response to injury-associated self-antigens, we looked for an antigen that would not induce an autoimmune disease. Candidate vaccines were the safe synthetic copolymer Cop-1, known to cross-react with self-antigens, or altered myelin-derived peptides. Using these compounds as vaccines, we could safely boost the protective autoimmune response in animal models of acute and chronic insults of mechanical or biochemical origin. Since this vaccination is effective even when given after the insult, and because it protects against the toxicity of glutamate (the most common mediator of secondary degeneration), it can be used to treat chronic neurodegenerative disorders such as glaucoma, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis.

MeSH Terms
Acute Disease Animals Autoantigens/immunology Chronic Disease Humans Immune System/drug effects,immunology Immunotherapy, Active/methods,trends Inflammation/drug therapy,immunology Neurodegenerative Diseases/drug therapy,immunology,physiopathology Neuroprotective Agents/immunology T-Lymphocytes/drug effects,immunology
Chemicals
Autoantigens Neuroprotective Agents
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Schwartz M
Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel. [email protected]
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Article Info
Journal
Cellular and molecular neurobiology
Abbr.
Cell Mol Neurobiol
ISSN
0272-4340
DOI
10.1023/a:1015139718466
Email
[email protected]
Published
2001-12-00
Pages
617-27
Language
English
Region
United States
NLM ID
8200709
Subset
IM
External Links
PubMed source DOI: 10.1023/a:1015139718466 View journal details
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