Τίτλος:
Novel Approaches in the Immunotherapy of Multiple Sclerosis: Cyclization of Myelin Epitope Peptides and Conjugation with Mannan
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Multiple Sclerosis (MS) is a serious autoimmune disease. The patient in an advanced state of the disease has restrained mobility and remains handicapped. It is therefore understandable that there is a great need for novel drugs and vaccines for the treatment of MS. Herein we summarise two major approaches applied for the treatment of the disease using peptide molecules alone or conjugated with mannan. The first approach focuses on selective myelin epitope peptide or peptide mimetic therapy alone or conjugated with mannan, and the second on immune-therapy by preventing or controlling disease through the release of appropriate cytokines. In both approaches the use of cyclic peptides offers the advantage of increased stability from proteolytic enzymes. In these approaches, the synthesis of myelin epitope peptides conjugated to mannan is of particular interest as this was found to protect mice against experimental autoimmune encephalomyelitis, an animal model of MS, in prophylactic and therapeutic protocols. Protection was peptide-specific and associated with reduced antigen-specific T cell proliferation. The aim of the studies of these peptide epitope analogs is to understand their molecular basis of interactions with human autoimmune T-cell receptor and a MS-associated human leucocyte antigen (HLA)-DR2b. This knowledge will lead the rational design to new beneficial non-peptide mimetic analogs for the treatment of MS. Some issues of the use of nanotechnology will also be addressed as a future trend to tackle the disease. We highlight novel immunomodulation and vaccine-based research against MS based on myelin epitope peptides and strategies developed in our laboratories. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Συγγραφείς:
Matsoukas, J.M.
Ligielli, I.
Chasapis, C.T.
Kelaidonis, K.
Apostolopoulos, V.
Mavromoustakos, T.
Περιοδικό:
Brain Sciences
Λέξεις-κλειδιά:
amyloid beta protein; cell penetrating peptide; cytokine; epitope; exendin 4; gamma interferon; immunoglobulin G; interleukin 4; leukocyte antigen; mannan; myelin; myelin basic protein; myelin oligodendrocyte glycoprotein; polymer; proteinase; T lymphocyte receptor; vaccine, Alzheimer disease; amino acid sequence; antibody response; antigen presenting cell; autoimmune disease; autoimmunity; blood brain barrier; CD4+ T lymphocyte; cell differentiation; cell proliferation; central nervous system; circular dichroism; conjugation; crystal structure; cyclization; cytokine release; cytotoxicity; degenerative disease; demyelination; dendritic cell; drug delivery system; encephalomyelitis; experimental autoimmune encephalomyelitis; human; humoral immunity; hydrogen bond; hypertension; immunogenicity; molecular model; multiple sclerosis; myelooptic neuropathy; nerve degeneration; neuroprotection; nonhuman; nuclear magnetic resonance imaging; peptide synthesis; peripheral blood mononuclear cell; regulatory T lymphocyte; remyelinization; Review; T lymphocyte activation; vaccination
DOI:
10.3390/brainsci11121583
