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1.
Br J Pharmacol ; 172(7): 1769-82, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25521311

RESUMO

BACKGROUND AND PURPOSE: Selective agonists of the sigma-1 receptor (σ1 protein) are generally reported to protect against neuronal damage and modulate oligodendrocyte differentiation. Human and rodent lymphocytes possess saturable, high-affinity binding sites for compounds binding to the σ1 protein and potential immunomodulatory properties have been described for σ1 protein ligands. Experimental autoimmune encephalomyelitis (EAE) is recognized as a valuable model of the inflammatory aspects of multiple sclerosis (MS). Here, we have assessed the role of a σ1 protein agonist, containing the tetrahydroisoquinoline-hydantoin structure, in EAE. EXPERIMENTAL APPROACH: EAE was induced in SJL/J female mice by active immunization with myelin proteolipid protein (PLP)139-151 peptide. The σ1 protein agonist was injected i.p. at the time of immunization (day 0). Disease severity was assessed clinically and by histopathological evaluation of the CNS. Phenotyping of B-cell subsets and regulatory T-cells were performed by flow cytometry in spleen and cervical lymph nodes. KEY RESULTS: Prophylactic treatment of EAE mice with the σ1 protein agonist prevented mononuclear cell accumulation and demyelination in brain and spinal cord and increased T2 B-cells and regulatory T-cells, resulting in an overall reduction in the clinical progression of EAE. CONCLUSIONS AND IMPLICATIONS: This σ1 protein agonist, containing the tetrahydroisoquinoline-hydantoin structure, decreased the magnitude of inflammation in EAE. This effect was associated with increased proportions of B-cell subsets and regulatory T-cells with potential immunoregulatory functions. Targeting of the σ1 protein might thus provide new therapeutic opportunities in MS.


Assuntos
Encefalomielite Autoimune Experimental/tratamento farmacológico , Esclerose Múltipla/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Receptores sigma/agonistas , Animais , Linfócitos B/imunologia , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Citocinas/sangue , Encefalomielite Autoimune Experimental/sangue , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/patologia , Feminino , Imunoglobulina G/sangue , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia , Camundongos , Esclerose Múltipla/sangue , Esclerose Múltipla/imunologia , Esclerose Múltipla/patologia , Proteína Proteolipídica de Mielina/imunologia , Fármacos Neuroprotetores/farmacologia , Fragmentos de Peptídeos/imunologia , Medula Espinal/efeitos dos fármacos , Medula Espinal/patologia , Baço/efeitos dos fármacos , Baço/imunologia , Linfócitos T Reguladores/imunologia , Receptor Sigma-1
2.
Bull Soc Pathol Exot ; 105(4): 276-83, 2012 Oct.
Artigo em Francês | MEDLINE | ID: mdl-22886432

RESUMO

The impact of autoimmunity on malaria-infection evolution reported by various works has led us to compare reactive patterns of self-dependent systemic IgG from 54 patients aged less than 15 years old to those from 46 subjects older than 15 years. These subjects were divided into 34 Plasmodium falciparum asymptomatic carriers (ACs), 30 cases of uncomplicated malaria (UM), and 36 patients suffering from cerebral malaria (CM) living in the same endemic area. The reactivity of the plasma antibodies against human brain tissue extract was assessed by western blotting. Comparative analysis of reactive bands (linear discriminant analysis, LDA) revealed the existence of patterns that distinguish, among the more susceptible subjects aged less than 15 years old, the different clinical forms. In contrast, in less susceptible subjects aged more than 15 years old, the patterns are homogenous and do not allow the separation of these clinical forms. This self-reactive repertoire might be witnessed as an imprint of the clinical tolerance acquired during the years of living in endemic areas. The singularity of this profile under the age of 15 years might have a prognostic value.


Assuntos
Envelhecimento/imunologia , Autoanticorpos/imunologia , Imunoglobulina G/imunologia , Malária Cerebral/imunologia , Malária Falciparum/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Especificidade de Anticorpos , Autoanticorpos/sangue , Autoantígenos/imunologia , Encéfalo/imunologia , Portador Sadio/epidemiologia , Portador Sadio/imunologia , Criança , Pré-Escolar , Côte d'Ivoire/epidemiologia , Progressão da Doença , Suscetibilidade a Doenças , Doenças Endêmicas , Exposição Ambiental , Feminino , Humanos , Tolerância Imunológica , Imunoglobulina G/sangue , Lactente , Malária Cerebral/epidemiologia , Malária Cerebral/etiologia , Malária Falciparum/epidemiologia , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/imunologia , Prognóstico , Adulto Jovem
4.
Horm Res Paediatr ; 74(4): 275-84, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20453472

RESUMO

BACKGROUND: Autoimmune polyendocrine syndrome type 1 (APS1) has been poorly evaluated in France. We focused on the north-western part of the country to describe clinical phenotypes, especially severe forms of the disease, and AIRE gene mutations. METHODS: Clinical and immunological data were collected, and pathological mutations were identified by DNA sequencing. RESULTS: Nineteen patients were identified with APS1. Clinical manifestations varied greatly, showing 1-10 components. Mucocutaneous candidiasis, adrenal failure, hypoparathyroidism, alopecia and other severe infections were the most frequent components. Four patients had severe forms, needing immunosuppressive therapy: 2 for hepatitis; 1 for severe malabsorption, and 1 for a T cell large granular lymphocytic leukemia. These therapies were very effective but caused general discomfort. One patient died of septicemia. Four different AIRE gene mutations were identified, and a 13-bp deletion in exon 8 (c.967-979del13) was the most prevalent. There was at least one allele correlating with this mutation and alopecia occurrence (p = 0.003). No novel mutation was detected. CONCLUSION: APS1 appears to be rare in north-western France. We identified 4 cases with a severe form needing immunosuppressive therapy. The AIRE gene mutations are more like those found in north-western Europe than those found in Finland.


Assuntos
Terapia de Imunossupressão , Polimorfismo Genético , Fatores de Transcrição/genética , Adolescente , Adulto , Alopecia/epidemiologia , Alopecia/genética , Criança , Análise Mutacional de DNA , Feminino , França/epidemiologia , Genótipo , Humanos , Imunossupressores , Masculino , Pessoa de Meia-Idade , Mutação , Fenótipo , Poliendocrinopatias Autoimunes/epidemiologia , Poliendocrinopatias Autoimunes/genética , Poliendocrinopatias Autoimunes/fisiopatologia , Poliendocrinopatias Autoimunes/terapia , Índice de Gravidade de Doença , Adulto Jovem , Proteína AIRE
5.
Mult Scler ; 15(5): 593-600, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19299435

RESUMO

OBJECTIVE: We previously showed that serum IgG repertoires distinguished multiple sclerosis (MS) patients from healthy subjects and from patients with other inflammatory neurological diseases (OIND). We questioned whether the serum IgG repertoire of patients presenting a clinically isolated syndrome (CIS) could predict MS. METHODS: The global IgG immune responses against brain antigens in sera from 50 CIS patients were evaluated by immunoblotting. The IgG reactivities were compared with those from MS sera (n = 82), healthy sera (n = 27), and sera from OIND (n = 42). A linear discriminant analysis (LDA) defined a score for each individual. RESULTS: About 78% of scores obtained from CIS patients were located in the "MS area." During the follow-up (3.5 +/- 1.3 years), 28 patients fulfilled the McDonald criteria for MS, 15 patients remained CIS, and 7 patients developed OIND. Among the patients with an LDA score in the "MS area," 61.5% converted to MS. DISCUSSION: Our results suggest that a pathological distortion of the self-reactive IgG repertoire occurs early so that immunomodulating treatment should be started as early as possible; they also highlight the early involvement of B cells in the physiopathological process in MS.


Assuntos
Linfócitos B/imunologia , Biomarcadores/sangue , Imunoglobulina G/sangue , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/imunologia , Especificidade de Anticorpos , Encéfalo/imunologia , Feminino , Humanos , Masculino , Proteínas do Tecido Nervoso/imunologia , Valor Preditivo dos Testes , Fatores de Risco , Estudos Soroepidemiológicos
6.
Rev Med Interne ; 30(4): 316-21, 2009 Apr.
Artigo em Francês | MEDLINE | ID: mdl-19195743

RESUMO

INTRODUCTION: Acute alcoholic intoxications (AAI) are frequent in hospitals. This entails some difficulties to caregivers and their clinical approach is little developed in France. This study aimed at estimating perception of alcohol consumption of hospitalized people with positive alcohol blood test at admission. Alcohol measurements were nonsystematic and ordered by a physician. Then this study assessed the role of a clinical interview the day after an AAI. METHODS: Each person admitted with a positive alcohol blood test was systematically met by a professional in addictology, referring to a procedure in process for 10 years in this hospital. A prospective collection of the data was performed during 2006. RESULTS: Nine hundred and seventy-three episodes were identified corresponding to 758 persons (78% of men and 22% of women). The average alcohol blood level was 2.06+/-1.18g/L. Eighty-five percent of those patients were admitted and 52% were interviewed. Damage due to alcohol was identified for 69% and a misuse of alcohol for 92% (19% abuse, 73% dependence according to the DSM IV), without significant correlation to alcohol blood level. CONCLUSION: Blood alcohol level assay at the hospital admission, when the test has been medically recommended, targets a misusing alcohol group of people. These patients need addictologic care, after a first toxicological stage. This study confirms that in such a case a discussion offer is possible and agreed by diseased people. This offer is a first step towards people who could not express explicitly their need for help and constitute an opportunity to care.


Assuntos
Intoxicação Alcoólica/epidemiologia , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/psicologia , Intoxicação Alcoólica/patologia , Intoxicação Alcoólica/psicologia , Alcoolismo/epidemiologia , Criança , Etanol/sangue , Feminino , França/epidemiologia , Hospitalização , Hospitais Gerais , Humanos , Masculino , Pessoa de Meia-Idade , Percepção , Razão de Masculinidade , Adulto Jovem
7.
Ann Rheum Dis ; 63(4): 415-9, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15020336

RESUMO

BACKGROUND: Anti-filaggrin antibodies (AFA) are among the most specific antibodies for rheumatoid arthritis, so procedures for their detection should be included in early biological diagnoses. AFA can be detected by indirect immunofluorescence (anti-keratin antibodies, AKA) or by new enzyme immunoassays (EIA). Their comparative performance needs to be established. OBJECTIVE: To compare these technical procedures to optimise the serological diagnosis of rheumatoid arthritis. METHODS: Results obtained using AKA and EIA were compared in 271 sera from 140 patients with rheumatoid arthritis at various stages, 98 patients with other autoimmune diseases, and 33 healthy subjects. EIA were successively undertaken with citrullinated linear filaggrin peptide (home made EIA) or cyclic citrullinated peptide (CCP2, commercial kits). Rheumatoid factor (RF) was assessed by EIA in all patients. RESULTS: Anti-CCP2 kits showed the best sensitivity and specificity (65% and 96%, respectively). Among the 140 patients with rheumatoid arthritis, those with very recent disease (less than six months' duration, n = 21) were studied as a separate group. In this group, the sensitivity of anti-CCP2 kits decreased to approximately 50%. Nevertheless this assay remained the most accurate when compared with AKA or home made EIA using linear filaggrin peptides. The combination of anti-CCP2 and RF only slightly increased the sensitivity of the diagnosis of very early rheumatoid arthritis. CONCLUSIONS: Kits using citrullinated cyclic peptides (CCP2) were more suitable than either AKA or EIA using linear filaggrin peptides for the diagnosis of early rheumatoid disease.


Assuntos
Anticorpos/sangue , Artrite Reumatoide/diagnóstico , Proteínas de Filamentos Intermediários/imunologia , Artrite Reumatoide/sangue , Artrite Reumatoide/imunologia , Biomarcadores/sangue , Citrulina/imunologia , Proteínas Filagrinas , Técnica Indireta de Fluorescência para Anticorpo/métodos , Humanos , Técnicas Imunoenzimáticas/métodos , Imunoglobulina G/sangue , Queratinas/imunologia , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/imunologia , Kit de Reagentes para Diagnóstico , Fator Reumatoide/análise , Fator Reumatoide/imunologia , Sensibilidade e Especificidade , Síndrome de Sjogren/sangue , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/imunologia
9.
J Neuroimmunol ; 129(1-2): 232, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12161040

RESUMO

We investigated the effects of interferon beta-1a (IFN beta-1a) on specific response towards two immunodominant MBP peptides and on global production of IgG. We evaluated 54 sera from multiple sclerosis (MS) patients at baseline and 1 year after treatment. We did not observe any modification of immune response to the MBP peptides but we noted a significant decrease in mean IgG concentrations in patients with progression of the disease but not in stable patients. These results suggest that IFN beta1a restores or maintains a beneficial immune response.


Assuntos
Regulação para Baixo/efeitos dos fármacos , Sistema Imunitário/efeitos dos fármacos , Imunoglobulina G/sangue , Imunoglobulina G/efeitos dos fármacos , Interferon beta/uso terapêutico , Esclerose Múltipla/sangue , Esclerose Múltipla/tratamento farmacológico , Adulto , Autoanticorpos/sangue , Autoanticorpos/efeitos dos fármacos , Progressão da Doença , Regulação para Baixo/imunologia , Epitopos/imunologia , Feminino , Humanos , Sistema Imunitário/imunologia , Interferon beta-1a , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/imunologia , Proteína Básica da Mielina/imunologia , Fragmentos de Peptídeos/imunologia , Resultado do Tratamento
10.
Eur Cytokine Netw ; 13(2): 200-6, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12101075

RESUMO

Interleukin-10 (IL-10) is a potent anti-inflammatory and immunosuppressive cytokine that modulates disease expression in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). In previous studies, two dinucleotide repeat elements (microsatellites G and R) were identified, respectively located about 1.1 and 4.0 kb upstream of the IL-10 gene transcription initiation site. Several of their alleles were found to be associated with the level of IL-10 production. The aim of our study was to determine whether sequence variations in the IL-10 gene were associated with MS susceptibility and progression. To do so, we analyzed the distribution of IL-10.R and IL-10.G alleles and genotype polymorphisms in MS patients and healthy controls. We then correlated our findings with disease severity in MS patients using the progression index (PI). Patients were classified as experiencing mild (PI < 0.5) or severe (PI > 0.5) disease progression. Our results show no association between the IL-10.R microsatellite and MS, regardless of disease severity. However, IL-10.G microsatellite genotyping showed that IL-10.G9/9, G10/13, G11/13 and G13/14 were more frequently found in patients with mild disease progression (p = 0.005). We also found that in patients with severe disease progression, IL-10.G9/10, G9/11, G9/13 and G12/13 were over-represented (p = 0.002). Our study indicates that neither the IL-10.R or the IL-10.G alleles are associated with predisposition to MS. However, several IL-10.G genotypes might emerge as markers of disease progression.


Assuntos
Interleucina-10/genética , Esclerose Múltipla/genética , Polimorfismo Genético , Regiões Promotoras Genéticas , Adolescente , Adulto , Idoso , Alelos , Sequência de Bases , Primers do DNA , Progressão da Doença , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Esclerose Múltipla/imunologia , Esclerose Múltipla/fisiopatologia , Valores de Referência
11.
J Neuroimmunol ; 117(1-2): 149-55, 2001 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-11431015

RESUMO

An increased level of citrullinated myelin basic protein (MBP-C8) has been reported in the brains of multiple sclerosis (MS) patients. However, the involvement of the immune response to post-translational modified MBP in the pathophysiology of MS remains speculative. The aim of this study was to compare the levels of immunoglobulin G antibodies to several MBP epitopes, before and after citrullination, in the cerebrospinal fluid (CSF) and sera of MS patients using enzyme-linked immunosorbent assay (ELISA). We analyzed antibody reactivity against various MBP-peptides in the CSF and sera of 60 MS patients, and 30 patients with other neurological diseases (OND) as controls. The peptides tested were: MBP(75-98) (peptide 1), native (peptide 2) and citrullinated (peptide 3) MBP(108-126) (ARG(122)-->Cit(122)), and native (peptide 4) and citrullinated (peptide 5) MBP(151-170) (ARG(159, 170)-->Cit(159, 170)). All selected peptides could support an immune reactivity in CSF and sera of MS and OND patients. A higher reactivity against peptide 4 was found in the CSF of MS patients compared with OND patients (P<0.0001), but not against citrullinated peptides (peptides 3 and 5). However, we observed that the citrullination state of peptide 2 modified the patterns of immune reactivity more markedly in MS patients (P<0.0001) than in OND patients (P<0.02). Although some MBP epitopes could be a potential target in MS, our data did not demonstrate any difference of antibody response to MBP peptides in their citrullinated forms.


Assuntos
Citrulina/metabolismo , Imunoglobulina G/análise , Esclerose Múltipla/imunologia , Proteína Básica da Mielina/imunologia , Adolescente , Adulto , Idoso , Sequência de Aminoácidos , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Processamento de Proteína Pós-Traducional
12.
Biochem Biophys Res Commun ; 283(2): 437-44, 2001 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-11327721

RESUMO

A possible involvement of HTLV-1-related endogenous sequence 1 (HRES-1) in autoimmune diseases has been recently reported. In primate cells, PCRs and RT-PCRs using specific primers reveal the presence and the transcription of gag-related sequences. However antisera generated against selected HRES-1 peptides failed to detect a 28-kDa protein deduced from the translated gag ORF and described previously. Such discordant results led us to perform DNA cloning and sequencing of LTR- and gag-related nucleotidic fragments. Repeated sequence analyses on distinct samples revealed frameshift mutations in the gag and LTR ORFs. Our sequence analyses detected a stop codon in the gag-related ORF, which is inconsistent with the expression of a 28-kDa protein. Instead of the two ORFs previously found, our gag-related region contained three ORFs. One of them demonstrated higher nucleotidic and peptidic homologies with the p19 gag of HTLV-I. However, the molecular analyses of our new sequence did not show evidence of potent translation capacities.


Assuntos
Autoantígenos/genética , Doenças Autoimunes/imunologia , Doenças Autoimunes/virologia , Retrovirus Endógenos/genética , Retrovirus Endógenos/imunologia , Mutação da Fase de Leitura , Sequência de Aminoácidos , Autoantígenos/química , Doenças Autoimunes/genética , Sequência de Bases , Biomarcadores , Estudos de Casos e Controles , DNA/genética , Primers do DNA/genética , Retrovirus Endógenos/patogenicidade , Genes gag , Dados de Sequência Molecular , Peso Molecular , Fases de Leitura Aberta , RNA Mensageiro/genética , Homologia de Sequência de Aminoácidos , Homologia de Sequência do Ácido Nucleico , Sequências Repetidas Terminais
13.
J Occup Environ Med ; 43(3): 289-94, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11285878

RESUMO

A back school was established in 1992 at the University Hospital of Lille (France) for employees with low back pain. We report its medical and socioeconomic benefits with a mean time to follow-up of 4 years. Our retrospective study included 108 health care workers and provides objective data (absenteeism, use of health care) and subjective information (progression of pain and disorder, social and professional impact) before training and a mean of 4 years after training. We found that 92% of the participants were satisfied with the training and that back pain had regressed or resolved for 55% of them. Both the frequency and duration of pain had decreased significantly. Seventy percent continue to apply the advice they received in their everyday life. Dealing with the problems specific to professional activities contributed to reduce the strain experienced on the job by the health care workers and improved their satisfaction at work. Global absenteeism was reduced by 57.8%, whereas it was reduced by 33% for back pain alone 4 years after implementing this program. Our study provides evidence of the positive impact of this type of training on the way back pain is perceived and on everyday life. The assessment of the cost/efficiency ratio completes the list of durable benefits reported here.


Assuntos
Pessoal Técnico de Saúde/educação , Dor nas Costas/reabilitação , Satisfação no Emprego , Serviços de Saúde do Trabalhador/organização & administração , Adulto , Feminino , Seguimentos , França , Hospitais Universitários , Humanos , Masculino , Estudos Retrospectivos
14.
Neuroreport ; 10(17): 3491-5, 1999 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-10619631

RESUMO

To evaluate the usefulness of tau proteins as biological markers in the diagnosis of dementia of the Alzheimer type (DAT), we analyzed the concentration of tau proteins in 253 cerebrospinal fluid (CSF) samples from patients with or without neurological disorders. Our study showed a significant increase of the mean CSF tau concentration in DAT patients compared with that from non-DAT patients. Interestingly, a significative decrease of CSF tau in patients with frontotemporal dementia was found. We also observed a positive correlation between the CSF-tau concentration and the number of apoepsilon4 alleles. The CSF apolipoprotein E concentration was evaluated and revealed no variation between the groups, although we observed a significant correlation between CSF tau and apolipoprotein E in DAT patients.


Assuntos
Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico , Apolipoproteínas E/líquido cefalorraquidiano , Demência/líquido cefalorraquidiano , Demência/diagnóstico , Proteínas tau/líquido cefalorraquidiano , Fatores Etários , Idade de Início , Idoso , Alelos , Análise de Variância , Apolipoproteína E4 , Apolipoproteínas E/genética , Diagnóstico Diferencial , Síndrome de Down/líquido cefalorraquidiano , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Fatores Sexuais
15.
J Neurochem ; 69(2): 834-44, 1997 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9231745

RESUMO

PHF-tau proteins are the major components of the paired helical filament (PHF) from Alzheimer's disease (AD) neurofibrillary lesions. They differ both qualitatively and quantitatively in their degree of phosphorylation when compared with native tau proteins. However, little is known about the extent and heterogeneity of phosphorylated sites or the isoform composition and the isoelectric variants of PHF-tau. Therefore, we have characterized PHF-tau proteins from cortical brain tissue homogenates of 13 AD patients using two-dimensional gel electrophoresis. Whatever the topographical origin of brain tissue homogenates, PHF-tau proteins shared the same two-dimensional gel electrophoresis profile made of a tau triplet of 55, 64, and 69 kDa. A 74-kDa hyperphosphorylated tau component was detected particularly in the youngest and most severely affected AD patients. This additional component of hyperphosphorylated tau was shown to correspond to the longest brain tau isoform. Furthermore, the isoelectric points of PHF-tau from older AD patients were significantly more basic, indicating a lower degree of phosphorylation. These results show that the severity of neurofibrillary degeneration of AD is modulated by age.


Assuntos
Envelhecimento , Doença de Alzheimer/metabolismo , Córtex Cerebral/química , Estrutura Secundária de Proteína , Proteínas tau/química , Idoso , Idoso de 80 Anos ou mais , Western Blotting , Eletroforese em Gel Bidimensional , Eletroforese em Gel de Poliacrilamida , Lobo Frontal/química , Hipocampo/química , Humanos , Concentração de Íons de Hidrogênio , Focalização Isoelétrica , Pessoa de Meia-Idade , Peso Molecular , Fosforilação , Lobo Temporal/química
16.
FEBS Lett ; 412(3): 578-82, 1997 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-9276470

RESUMO

Tau proteins aggregate into different neuronal inclusions in several neurodegenerative disorders. In Alzheimer's disease (AD), hyperphosphorylated Tau from paired helical filaments (PHF) of neurofibrillary tangles, named PHF-Tau, have an electrophoretic profile with four main bands (Tau 55, 64, 69, 74 kDa). In Pick's disease, phosphorylated Tau from Pick bodies are made of two major components (Tau 55, 64 kDa) and a minor 69 kDa. Here we show, using specific antibodies against translated exon 2, 3 or 10 of Tau isoforms, that the set of Tau isoforms engaged in the most insoluble part of PHF in AD is made of Tau isoforms with exon 10 while they are lacking in phosphorylated Tau from Pick's disease. Our results suggest that specific sets of Tau isoforms distinguish between typical neuronal inclusions.


Assuntos
Doença de Alzheimer/metabolismo , Demência/metabolismo , Proteínas tau/metabolismo , Doença de Alzheimer/patologia , Western Blotting , Demência/patologia , Eletroforese em Gel Bidimensional , Humanos , Isomerismo , Peso Molecular , Emaranhados Neurofibrilares/química , Emaranhados Neurofibrilares/metabolismo , Emaranhados Neurofibrilares/patologia , Fosforilação , Proteínas tau/química
17.
Neurosci Lett ; 212(2): 91-4, 1996 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-8832646

RESUMO

Apolipoprotein E (Apo E), one of the major structural and functional apolipoproteins, has recently been implicated in the pathogenesis of Alzheimer's disease (AD). Several studies revealed that Apo E4 isoform is associated with the pathogenic process in AD. A significant reduction of cerebrospinal fluid (CSF) Apo E level in AD patients has been reported in two studies. To further investigate the physiopathological significance of such a variation of Apo E concentration in the CSF, we performed a quantification of Apo E by an enzyme linked immunosorbent assay (ELISA). There were no significant differences in CSF Apo E level between AD cases and control subjects or patients suffering from other neurological diseases. Gender, age and Apo E phenotype explained none of CSF Apo E concentration variability.


Assuntos
Doença de Alzheimer/líquido cefalorraquidiano , Apolipoproteínas E/líquido cefalorraquidiano , Idoso , Alelos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais
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