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A novel neurotherapeutic for multiple sclerosis, ischemic injury, methamphetamine addiction, and traumatic brain injury
by
Vandenbark, Arthur A.
, Benedek, Gil
, Meza-Romero, Roberto
, Offner, Halina
in
Addictions
/ Amphetamine abuse
/ Amphetamine-Related Disorders - therapy
/ Analysis
/ Animal models
/ Animals
/ Anti-Inflammatory Agents - therapeutic use
/ Antigen receptors, T cell
/ Biomedical and Life Sciences
/ Biomedicine
/ Blood-brain barrier
/ Brain
/ Brain Injuries, Traumatic - therapy
/ Brain Ischemia - therapy
/ Central nervous system
/ Cerebral ischemia
/ Chemokines
/ Chloride-Bicarbonate Antiporters
/ Copyright
/ Cytokines
/ Dendritic cells
/ Dopachrome isomerase
/ Drug abuse
/ Drug development
/ Drug therapy
/ Health aspects
/ Humans
/ Immunology
/ Inflammation
/ Injuries
/ Ischemia
/ Ischemic injury
/ Leukocyte migration
/ Leukocytes (mononuclear)
/ Lymphocytes
/ Macrophage migration inhibitory factor
/ Major histocompatibility complex
/ Medical research
/ Medicine, Experimental
/ Methamphetamine
/ Methamphetamine addiction
/ Microglia
/ Monocytes
/ Multiple sclerosis
/ Multiple Sclerosis - therapy
/ Myelin-Oligodendrocyte Glycoprotein - therapeutic use
/ Nervous system
/ Neurobiology
/ Neuroimmunology
/ Neurology
/ Neurosciences
/ Oligodendrocyte-myelin glycoprotein
/ Peptide Fragments - therapeutic use
/ Peptides
/ Proteins
/ Psychopharmacology
/ Receptors
/ Review
/ Rodents
/ Spinal cord
/ Substance abuse treatment
/ Sulfate Transporters
/ T cell receptors
/ T cells
/ Trauma
/ Traumatic brain injury
/ Tumor necrosis factor-TNF
2019
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A novel neurotherapeutic for multiple sclerosis, ischemic injury, methamphetamine addiction, and traumatic brain injury
by
Vandenbark, Arthur A.
, Benedek, Gil
, Meza-Romero, Roberto
, Offner, Halina
in
Addictions
/ Amphetamine abuse
/ Amphetamine-Related Disorders - therapy
/ Analysis
/ Animal models
/ Animals
/ Anti-Inflammatory Agents - therapeutic use
/ Antigen receptors, T cell
/ Biomedical and Life Sciences
/ Biomedicine
/ Blood-brain barrier
/ Brain
/ Brain Injuries, Traumatic - therapy
/ Brain Ischemia - therapy
/ Central nervous system
/ Cerebral ischemia
/ Chemokines
/ Chloride-Bicarbonate Antiporters
/ Copyright
/ Cytokines
/ Dendritic cells
/ Dopachrome isomerase
/ Drug abuse
/ Drug development
/ Drug therapy
/ Health aspects
/ Humans
/ Immunology
/ Inflammation
/ Injuries
/ Ischemia
/ Ischemic injury
/ Leukocyte migration
/ Leukocytes (mononuclear)
/ Lymphocytes
/ Macrophage migration inhibitory factor
/ Major histocompatibility complex
/ Medical research
/ Medicine, Experimental
/ Methamphetamine
/ Methamphetamine addiction
/ Microglia
/ Monocytes
/ Multiple sclerosis
/ Multiple Sclerosis - therapy
/ Myelin-Oligodendrocyte Glycoprotein - therapeutic use
/ Nervous system
/ Neurobiology
/ Neuroimmunology
/ Neurology
/ Neurosciences
/ Oligodendrocyte-myelin glycoprotein
/ Peptide Fragments - therapeutic use
/ Peptides
/ Proteins
/ Psychopharmacology
/ Receptors
/ Review
/ Rodents
/ Spinal cord
/ Substance abuse treatment
/ Sulfate Transporters
/ T cell receptors
/ T cells
/ Trauma
/ Traumatic brain injury
/ Tumor necrosis factor-TNF
2019
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A novel neurotherapeutic for multiple sclerosis, ischemic injury, methamphetamine addiction, and traumatic brain injury
by
Vandenbark, Arthur A.
, Benedek, Gil
, Meza-Romero, Roberto
, Offner, Halina
in
Addictions
/ Amphetamine abuse
/ Amphetamine-Related Disorders - therapy
/ Analysis
/ Animal models
/ Animals
/ Anti-Inflammatory Agents - therapeutic use
/ Antigen receptors, T cell
/ Biomedical and Life Sciences
/ Biomedicine
/ Blood-brain barrier
/ Brain
/ Brain Injuries, Traumatic - therapy
/ Brain Ischemia - therapy
/ Central nervous system
/ Cerebral ischemia
/ Chemokines
/ Chloride-Bicarbonate Antiporters
/ Copyright
/ Cytokines
/ Dendritic cells
/ Dopachrome isomerase
/ Drug abuse
/ Drug development
/ Drug therapy
/ Health aspects
/ Humans
/ Immunology
/ Inflammation
/ Injuries
/ Ischemia
/ Ischemic injury
/ Leukocyte migration
/ Leukocytes (mononuclear)
/ Lymphocytes
/ Macrophage migration inhibitory factor
/ Major histocompatibility complex
/ Medical research
/ Medicine, Experimental
/ Methamphetamine
/ Methamphetamine addiction
/ Microglia
/ Monocytes
/ Multiple sclerosis
/ Multiple Sclerosis - therapy
/ Myelin-Oligodendrocyte Glycoprotein - therapeutic use
/ Nervous system
/ Neurobiology
/ Neuroimmunology
/ Neurology
/ Neurosciences
/ Oligodendrocyte-myelin glycoprotein
/ Peptide Fragments - therapeutic use
/ Peptides
/ Proteins
/ Psychopharmacology
/ Receptors
/ Review
/ Rodents
/ Spinal cord
/ Substance abuse treatment
/ Sulfate Transporters
/ T cell receptors
/ T cells
/ Trauma
/ Traumatic brain injury
/ Tumor necrosis factor-TNF
2019
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A novel neurotherapeutic for multiple sclerosis, ischemic injury, methamphetamine addiction, and traumatic brain injury
Journal Article
A novel neurotherapeutic for multiple sclerosis, ischemic injury, methamphetamine addiction, and traumatic brain injury
2019
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Overview
Neurovascular, autoimmune, and traumatic injuries of the central nervous system (CNS) all have in common an initial acute inflammatory response mediated by influx across the blood-brain barrier of activated mononuclear cells followed by chronic and often progressive disability. Although some anti-inflammatory therapies can reduce cellular infiltration into the initial lesions, there are essentially no effective treatments for the progressive phase. We here review the successful treatment of animal models for four separate neuroinflammatory and neurodegenerative CNS conditions using a single partial MHC class II construct called DRa1-hMOG-35-55 or its newest iteration, DRa1(L50Q)-hMOG-35-55 (DRhQ) that can be administered without a need for class II tissue type matching due to the conserved DRα1 moiety of the drug. These constructs antagonize the cognate TCR and bind with high affinity to their cell-bound CD74 receptor on macrophages and dendritic cells, thereby competitively inhibiting downstream signaling and pro-inflammatory effects of macrophage migration inhibitory factor (MIF) and its homolog,
d
-dopachrome tautomerase (D-DT=MIF-2) that bind to identical residues of CD74 leading to progressive disease. These effects suggest the existence of a common pathogenic mechanism involving a chemokine-driven influx of activated monocytes into the CNS tissue that can be reversed by parenteral injection of the DRa1-MOG-35-55 constructs that also induce anti-inflammatory macrophages and microglia within the CNS. Due to their ability to block this common pathway, these novel drugs appear to be prime candidates for therapy of a wide range of neuroinflammatory and neurodegenerative CNS conditions.
Publisher
BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
Subject
/ Amphetamine-Related Disorders - therapy
/ Analysis
/ Animals
/ Anti-Inflammatory Agents - therapeutic use
/ Biomedical and Life Sciences
/ Brain
/ Brain Injuries, Traumatic - therapy
/ Chloride-Bicarbonate Antiporters
/ Humans
/ Injuries
/ Ischemia
/ Macrophage migration inhibitory factor
/ Major histocompatibility complex
/ Multiple Sclerosis - therapy
/ Myelin-Oligodendrocyte Glycoprotein - therapeutic use
/ Oligodendrocyte-myelin glycoprotein
/ Peptide Fragments - therapeutic use
/ Peptides
/ Proteins
/ Review
/ Rodents
/ T cells
/ Trauma
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