Abstract:
:Multiple sclerosis (MS) is a demyelinating and degenerative disease of the central nervous system (CNS) with a strong inflammatory component that affects more than 2 million people worldwide (and at least 400,000 in the United States). In MS, macrophage migration inhibitory factor (MIF) and D-dopachrome tautomerase (D-DT) enhance the inflammatory event as a result of their interaction with their cognate receptor CD74. Therefore, the search for new agents aimed at blocking this interaction is critical for therapeutic purposes and will be of paramount importance for the treatment of MS. DRα1-MOG-35-55 constructs have been demonstrated to be effective in the treatment of experimental autoimmune encephalomyelitis (EAE) a mouse model for MS. This effect is directly correlated with the binding to its cell surface receptor, CD74, apparently preventing or blocking the binding of two inflammatory factors, MIF and D-DT. Here we report that a single amino acid substitution (L50Q) in the DRα1 domain of the human and mouse DRα1-MOG-35-55 constructs (notated as DRhQ and DRmQ, respectively) possessed increased affinity for CD74, a greater capacity to block MIF binding, the ability to inhibit pERK1/2 signaling and increased therapeutic activity in mice with EAE. These data suggest that binding affinity for CD74 could serve as an in vitro indicator of biological potency of DRhQ and thus support its possible clinical utility as an effective therapy for MS and perhaps other diseases in which there is an inflammatory reaction driven by MIF and D-DT.
journal_name
Metab Brain Disjournal_title
Metabolic brain diseaseauthors
Meza-Romero R,Benedek G,Gerstner G,Kent G,Nguyen H,Offner H,Vandenbark AAdoi
10.1007/s11011-018-0331-2subject
Has Abstractpub_date
2019-02-01 00:00:00pages
153-164issue
1eissn
0885-7490issn
1573-7365pii
10.1007/s11011-018-0331-2journal_volume
34pub_type
杂志文章abstract::Following axonal interruption, structural, metabolic and physiological parameters change in motorneurons. Also, glial cells are involved in this process. Microglia proliferate and express new proteins such as vimentin or MHC antigens. Astrocytes show hypertrophy, increased GFAP synthesis, and formation of lamellae. Bo...
journal_title:Metabolic brain disease
pub_type: 杂志文章,评审
doi:10.1007/BF00999498
更新日期:1989-03-01 00:00:00
abstract::We investigated the biochemical alterations of the striatum of mice subjected to seven experimental schedules with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) treatment. The mice were treated intraperitoneally (i.p.) with MPTP (20 mg/kg in saline) four times a day at 2-hr intervals showed severe ...
journal_title:Metabolic brain disease
pub_type: 杂志文章
doi:10.1007/s11011-010-9195-9
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abstract::Today, neurological disorders such as epilepsy, depression, tardive dyskinesia, and stress, and neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, dementia, and Huntington's disease affect millions of people all over the world. Existing pharmacological interventions do not meet the desired t...
journal_title:Metabolic brain disease
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doi:10.1007/s11011-019-00400-9
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abstract::Autism (MIM 209850) is a heterogeneous neurodevelopmental disease that manifests within the first 3 years of life. Numerous articles reported that dysfunctional folate-methionine pathway enzymes may play an important role in the pathophysiology of autism. Methylenetetrahydrofolate reductase (MTHFR) is a critical enzym...
journal_title:Metabolic brain disease
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s11011-016-9815-0
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abstract::Hyperphenylalaninemia (HPA) leads to increased oxidative stress in patients with phenylketonuria (PKU) and in animal models of PKU. Early diagnosis and immediate adherence to a phenylalanine-restricted diet prevents HPA and, consequently, severe brain damage. However, treated adolescent and adult PKU patients have dif...
journal_title:Metabolic brain disease
pub_type: 杂志文章,评审
doi:10.1007/s11011-013-9414-2
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journal_title:Metabolic brain disease
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doi:10.1007/s11011-009-9136-7
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journal_title:Metabolic brain disease
pub_type: 杂志文章,评审
doi:10.1007/BF01999765
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journal_title:Metabolic brain disease
pub_type: 杂志文章
doi:10.1007/s11011-015-9704-y
更新日期:2015-12-01 00:00:00
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journal_title:Metabolic brain disease
pub_type: 杂志文章
doi:10.1007/BF00999385
更新日期:1986-06-01 00:00:00
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journal_title:Metabolic brain disease
pub_type: 杂志文章
doi:10.1007/s11011-015-9689-6
更新日期:2015-10-01 00:00:00
abstract::Stroke is the leading cause of disability among adults as well as the 2nd leading cause of death globally. Ischemic stroke accounts for about 85% of strokes, and currently, tissue plasminogen activator (tPA), whose therapeutic window is limited to up to 4.5 h for the appropriate population, is the only FDA approved dr...
journal_title:Metabolic brain disease
pub_type: 杂志文章,评审
doi:10.1007/s11011-020-00573-8
更新日期:2020-08-01 00:00:00
abstract::Chronic liver disease (CLD) leads to a spectrum of neuropsychiatric disorders named hepatic encephalopathy (HE). Even though brain energy metabolism is believed to be altered in chronic HE, few studies have explored energy metabolism in CLD-induced HE, and their findings were inconsistent. The aim of this study was to...
journal_title:Metabolic brain disease
pub_type: 杂志文章
doi:10.1007/s11011-015-9715-8
更新日期:2016-12-01 00:00:00
abstract::Hepatic encephalopathy (HE) represents a nervous system disorder caused due to liver dysfunction. HE is broadly classified as acute/overt and moderate-minimal HE. Since HE syndrome severely affects quality of life of the patients and it may be life threatening, it is important to develop effective therapeutic strategy...
journal_title:Metabolic brain disease
pub_type: 杂志文章
doi:10.1007/s11011-014-9556-x
更新日期:2014-12-01 00:00:00
abstract::The regional energy status and the availability of metabolic substrates during brain development are important, since a variety of fetal metabolic insults have been increasingly implicated in the evolution of neonatal brain disorders. The response of the brain to a metabolic insult is determined, in large part, by the...
journal_title:Metabolic brain disease
pub_type: 杂志文章
doi:10.1023/a:1025503115837
更新日期:2003-09-01 00:00:00
abstract::To assess whether EGb761 could protect elderly diabetic mice with cognitive disorders and explore the role of beclin-1-mediated autophagy in these protective effects. Two-month-old male db/db-/- mice and wild-type C57/BL6 mice were randomly divided into six groups: db/db-/- control, db/db-/- 50 mg, db/db-/- 100 mg, wi...
journal_title:Metabolic brain disease
pub_type: 杂志文章
doi:10.1007/s11011-018-0295-2
更新日期:2018-12-01 00:00:00
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journal_title:Metabolic brain disease
pub_type: 杂志文章
doi:10.1007/s11011-017-0141-y
更新日期:2018-02-01 00:00:00
abstract::Soluble amyloid-β protein (Aβ) oligomers have been recognized to be early and key intermediates in Alzheimer's disease-related synaptic dysfunction. In this study, using in vitro electrophysiology, we investigated interactions of the acidic oligosaccharide sugar chain (AOSC), a marine-derived acidic oligosaccharide, w...
journal_title:Metabolic brain disease
pub_type: 杂志文章
doi:10.1007/s11011-014-9521-8
更新日期:2014-09-01 00:00:00
abstract::Glutamate neurotoxicity was studied in primary neuronal cultures prepared from rat cerebral cortex and hippocampal CA1 sector. Neurons were cultivated with 5% native horse serum and then exposed to 0.1 or 1.0 mM glutamate for 5 min. Subsequently, neurons were allowed to recover for 24 hours either in the presence or i...
journal_title:Metabolic brain disease
pub_type: 杂志文章
doi:10.1007/BF02098880
更新日期:1994-12-01 00:00:00
abstract::Although gaseous ammonia (NH3) can freely enter cells through the plasma membrane where NH3 is cyto(neuro)toxic, NH3 and ionic ammonia (NH4+) contents have not been studied in biological materials. We developed a new method for measurement of expiratory NH3 concentration, which may reflect blood NH3 concentrations. Th...
journal_title:Metabolic brain disease
pub_type: 临床试验,杂志文章
doi:
更新日期:1997-06-01 00:00:00
abstract::The availability of an animal model is crucial in studying the pathophysiological mechanisms of disease and to test possible therapies. Now, there are several models for the study of liver diseases, but there still remains a lack of a satisfactory animal model of chronic liver disease with hepatic encephalopathy (HE) ...
journal_title:Metabolic brain disease
pub_type: 杂志文章,评审
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journal_title:Metabolic brain disease
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journal_title:Metabolic brain disease
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doi:10.1007/s11011-019-00511-3
更新日期:2020-01-01 00:00:00
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journal_title:Metabolic brain disease
pub_type: 杂志文章
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更新日期:2020-06-01 00:00:00
abstract::The central nervous system is one of the most vulnerable organs affected by mercury toxicity. Both acute and chronic exposure to mercury is also known to cause a variety of neurological or psychiatric disorders. Here, the neuroprotective effect of berberine (BN; 100 mg/kg bwt) on mercuric chloride (HgCl2; 0.4 mg/kg bw...
journal_title:Metabolic brain disease
pub_type: 杂志文章
doi:10.1007/s11011-015-9652-6
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abstract::Hepatic encephalopathy (HE) is an important cause of morbidity and mortality in patients with severe liver disease. Although the molecular basis for the neurological disorder in HE remains elusive, elevated ammonia and its chief metabolite glutamine are believed to be important factors responsible for altered cerebral...
journal_title:Metabolic brain disease
pub_type: 杂志文章,评审
doi:10.1023/a:1011666612822
更新日期:2001-06-01 00:00:00
abstract::Stroke is devastating and a leading cause of morbidity and mortality worldwide. Cerebral ischemia-reperfusion and its subsequent reactive hyperemia lead to neuronal damage in the hippocampus and cognitive decline. Chrysin (5, 7-dihydroxyflavone) is a well-known member of the flavonoid family with antioxidant and neuro...
journal_title:Metabolic brain disease
pub_type: 杂志文章
doi:10.1007/s11011-019-00527-9
更新日期:2020-02-01 00:00:00
abstract::Overwhelming evidence suggests that microglia play an important role in ischemic injury and they polarize into two different phenotypes with distinct functions after ischemic stroke. We performed the present study to investigate whether L-3-n butylphthalide (NBP) has an effect on microglial polarization. Mice were sub...
journal_title:Metabolic brain disease
pub_type: 杂志文章
doi:10.1007/s11011-018-0307-2
更新日期:2018-12-01 00:00:00
abstract::While alcohol-induced psychotic disorder (AIPD) is well recognised, relatively little is known about the condition. We undertook a review of the literature to identify studies on the epidemiology, clinical manifestations, underlying neurobiology and treatment of AIPD. Few prospective studies have been conducted on AIP...
journal_title:Metabolic brain disease
pub_type: 杂志文章,评审
doi:10.1007/s11011-013-9457-4
更新日期:2014-06-01 00:00:00
abstract::Chronic neuroinflammation is strongly associated with AD and altered peripheral and central levels of chemokines and cytokines have been frequently described in those with AD. Given the increasing evidence of ethnicity-related differences in AD, it was of interest to determine if those altered chemokine and cytokine l...
journal_title:Metabolic brain disease
pub_type: 杂志文章
doi:10.1007/s11011-019-00512-2
更新日期:2020-01-01 00:00:00
abstract::Schizophrenia is one of the most disabling mental disorders that affects up to 1 % of the population worldwide. Although the causes of this disorder remain unknown, it has been extensively characterized by a broad range of emotional, ideational and cognitive impairments. Studies indicate that schizophrenia affects neu...
journal_title:Metabolic brain disease
pub_type: 杂志文章
doi:10.1007/s11011-013-9417-z
更新日期:2013-09-01 00:00:00