Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0848771 (neurological disability)
 928 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Induction of HSPs is a natural response of stressed cells that protects against many insults including acute ischemia. TRC051384, a novel compound belonging to substituted 2-propen-1-one class is a potent inducer of heat shock protein 70 (HSP70). The aim of this study was to investigate the ability of TRC051384 in reducing neuronal injury and disability upon delayed treatments (4 and 8 hours post ischemia onset) in a rat model of transient cerebral ischemia. Focal cerebral ischemia was produced in rats by occluding the MCA using the intra luminal suture technique. Rats subjected to 2 hours focal cerebral ischemia were administered by intra-peritoneal route, TRC051384 or vehicle every 2 hours for 48 hours, from 4th hour or 8th hour after onset of ischemia. Progression of infarct and edema was assessed up to 48 hours post ischemic insult using magnetic resonance imaging and the neurological disability and survival studied till 7 days. Here we show for the first time that treatment with TRC051384 significantly reduces stroke associated neuronal injury (87% reduction in area of penumbra recruited to infarct, and 25% reduction in brain edema) and disability in a rat model of transient ischemic stroke even when administered 8 hours post onset of ischemia. Significant improvement in survival (50% by day 2 and 67.3% by day 7) was observed with TRC051384 treatment initiated at 4 hours after ischemia onset. Induction of HSP70 by TRC051384 involves HSF1 activation and results in elevated chaperone and anti-inflammatory activity. These results show that TRC051384 has the potential to be developed as a novel pharmacological agent for the treatment of ischemic stroke.
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PMID:Delayed intervention in experimental stroke with TRC051384--a small molecule HSP70 inducer. 2116 46

Patients with hyperphenylalaninemia (HPA) are detected through newborn screening for phenylketonuria (PKU). HPA is known to be caused by deficiencies of the enzyme phenylalanine hydroxylase (PAH) or its cofactor tetrahydrobiopterin (BH4). Current guidelines for the differential diagnosis of HPA would, however, miss a recently described DNAJC12 deficiency. The co-chaperone DNAJC12 is, together with the 70kDa heat shock protein (HSP70), responsible for the proper folding of PAH. All DNAJC12-deficient patients investigated to date responded to a challenge with BH4 by lowering their blood phenylalanine levels. In addition, the patients presented with low levels of biogenic amine in CSF and responded to supplementation with BH4, L-dopa/carbidopa and 5-hydroxytryptophan. The phenotypic spectrum ranged from mild autistic features or hyperactivity to severe intellectual disability, dystonia and parkinsonism. Late diagnosis result in permanent neurological disability, while early diagnosed and treated patients develop normally. Molecular diagnostics for DNAJC12 variants are thus mandatory in all patients in which deficiencies of PAH and BH4 are genetically excluded.
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PMID:DNAJC12 deficiency: A new strategy in the diagnosis of hyperphenylalaninemias. 2917 66

Multiple sclerosis (MS) is a chronic disease of the central nervous system and one of the most common causes of neurological disability among those aged 20-40 years, particularly in women. Major histocompatibility complex (MHC) Class II genes are known to be involved in the development of MS. One of the important groups of this complex is the HSP gene family, especially HSP70, which is induced under stress conditions. The aim of the present case-control study was to determine the association between the heat shock protein 70 (HSP70) and risk of MS in Iranian patients by genotyping the rs1061581 gene polymorphism. A total of 50 relapsing-remitting MS (RRMS) patients and 50 healthy control subjects were considered for this study. Genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) method. PCR-RFLP results of twenty-five randomly selected samples were confirmed by DNA sequencing. Genotypic and allelic distributions were compared between the case and control groups. We observed no significant difference in the distribution of rs1061581 genotype and allele frequencies between RRMS patients and controls. In addition, there was no association between the HSP70 gene polymorphism and the clinical variables in the case group. Our data indicate that HSP70, in particular rs1061581, is unlikely to be involved in the susceptibility to or the severity of RRMS in Iranian patients. Further large prospective studies are required to confirm these findings.
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PMID:Heat Shock Protein 70 and The Risk of Multiple Sclerosis in The Iranian Population. 3012 9

Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system. It represents one of the main causes of neurological disability in young people. In MS, the autoimmune response is directed against myelin antigens but other possible bio-molecular markers are investigated. The aim of this work was, through an in silico study, the evaluation of the transcriptional modifications between healthy subjects and MS patients in six brain areas (corpus callosum, hippocampus, internal capsule, optic chiasm, frontal and parietal cortex) in order to identify genes representative of the disease. Our results show the upregulation of the Heat Shock Proteins (HSPs) HSPA1A, HSPA1B, HSPA7, HSPA6, HSPH1 and HSPA4L of the HSP70 family, among which HSPA1A and HSPA1B are upregulated in all the brain areas. HSP70s are molecular chaperones indispensable for protein folding, recently associated with immune system maintenance. The little overexpression of the HSPs protects the cells from stress but extreme upregulation can contribute to the MS pathogenesis. We also investigated the genes involved in the immune system that result in overall upregulation in the corpus callosum, hippocampus, internal capsule, optic chiasm and are absent in the cortex. Interestingly, the genes of the immune system and the HSP70s have comparable levels of expression.
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PMID:Could the Heat Shock Proteins 70 Family Members Exacerbate the Immune Response in Multiple Sclerosis? An in Silico Study. 3250 76