Proteinases in inflammatory demyelinating disease

Whitaker, John N.

doi:10.1007/bf00197298

Cited by 21 publications

(6 citation statements)

References 105 publications

(81 reference statements)

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“…A number of proteinases may degrade MBP, and renal proteinases are capable of further degrading the intermediate size and small peptides of MBP [26].…”

Section: Discussionmentioning

confidence: 99%

The presence of immunoreactive myelin basic protein peptide in urine of persons with multiple sclerosis

Whitaker

1987

Annals of Neurology

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A polyclonal antiserum has been produced that can detect nanogram amounts of myelin basic protein (MBP)-like material in unconcentrated human urine. The urinary immunoreactive material is cross-reactive with human MBP peptides 45-89 and 69-89, dialyzable, heat resistant, and is not artifact of either degradation of radioligand or salt effect. An octapeptide, MBP peptide 82-89, was demonstrated to be the smallest peptide containing the main epitope against which this antiserum was directed. This epitope differed from the major epitope recognized by antisera detecting MBP-like material in cerebrospinal fluid, implying that the MBP-like material is altered, presumably degraded, in the kidney. Results of gel filtration and high-performance liquid chromatography suggested a size of 1,000 daltons or less and a charge similar to that of human MBP peptide 80-89. In a group of 39 persons with multiple sclerosis, 48 with other neurological diseases, and 26 normal control subjects, the concentration of urinary MBP-like material, related to the concentration of urinary creatinine, was significantly higher in the multiple sclerosis group (22.0 ng MBP-like material/mg creatinine) than in the other neurological diseases or control groups, in which the values were 7.0 and 3.9 ng MBP-like material/mg creatinine, respectively. Variations in the level of MBP-like material appearing in the urine may provide a clinically feasible test for myelin damage. The precise identification of the chemical nature of the urinary MBP-like material may also furnish a means for further analyzing the in vivo catabolism of the potentially autoantigenic MBP.

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“…A number of proteinases may degrade MBP, and renal proteinases are capable of further degrading the intermediate size and small peptides of MBP [26].…”

Section: Discussionmentioning

confidence: 99%

The presence of immunoreactive myelin basic protein peptide in urine of persons with multiple sclerosis

Whitaker

1987

Annals of Neurology

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“…O processo autoimune na EM implica na ativação de células T por um ou mais antígenos da mielina (peptídeos da proteina básica de mielina) apresentadas por moléculas do complexo maior de histocompatibilidade da classe II (MHC II) na superfície de astrócitos, células da microglia e endoteliais no SNC 17,18 O interferon gama é o maior regulador da expressão do MHC II e produz ativação das células macrófagas ou gliais na produção do fator de necrose tumoral alfa, que tem efeito citotóxico nos oligodendrócitos [19][20][21] . O mecanismo de ação proposto para o interferon beta é de que este antagoniza a síntese do interferon gama 22 .…”

Section: Discussionunclassified

Interferon beta 1-a na esclerose múltipla: experiência de um ano em 62 pacientes

Tilbery¹,

Felipe²,

Moreira³

et al. 2000

Arq. Neuro-Psiquiatr.

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RESUMO -Relatamos os resultados de estudo com o interferon beta 1-a em 62 pacientes ambulatoriais com a forma remitente-recorrente da esclerose múltipla durante um ano. Os critérios de inclusão para este tratamento foram de escore do EDSS entre 0 e 5,5 e de pelo menos relato de dois surtos nos dois últimos anos. Administramos 3 milhões de unidades internacionais de interferon beta 1-a três vezes por semana. Os objetivos deste estudo foram verificar o efeito da medicação no número de surtos e avaliar a eficácia da droga na progressão da doença. O índice anual de surtos nos pacientes que não tomaram a medicação foi 1,32 e naqueles medicados 0,63. O escore do EDSS em pacientes não medicados foi 4,7 e naqueles com medicamento 2,0. O interferon beta 1-a foi bem tolerado e 85% dos pacientes completaram um ano de tratamento.PALAVRAS-CHAVE: interferon beta 1-a, esclerose múltipla, tratamento. Interferon beta 1-a in multiple sclerosis: experience of one year in 62 patientsABSTRACT -We report the results of a trial of interferon beta 1-a in 62 ambulatory patients with relapsingremitting multiple sclerosis. Entry criteria included EDSS of 0 to 5.5 and at least two exacerbations in the previous 2 years. The patients received 3 million international units by subcutaneous injections three times a week. The end points were differences in exacerbation rate and treatment effect on disease progression. The annual exacerbation rate for patients that did not take the interferon beta 1-a was 1.32 and for the patients under medication 0.63. The EDSS score in patients that did not take the mediaction was 4.7 and 2.0 for the patients with interferon beta 1-a. Interferon beta 1-a was well tolerated and 85% of patients completed 1 year treatment.KEY WORDS: interferon beta 1-a, multiple sclerosis, treatment.A esclerose múltipla (EM) é doença inflamatória e desmielinizante do sistema nervoso central. Admite-se que células T, ativadas por autoantígeno ainda não determinado, passam da periferia para o SNC pela barreira hematoencefálica, evento considerado essencial na patogênese da desmielinização 1,2 . Até o início da década passada, dispunhamos apenas de corticóides e imunossupressores para o tratamento de pacientes com EM entretanto, estes medicamentos apresentam resultados pouco eficazes e não evitam a progressão da doença 3,4 . Após os relatos de Jacobs e Munschauer 5 , inúmeros ensaios clínicos com interferon foram realizados até que ,em 1993, o FDA americano aprovou e autorizou seu uso em pacientes portadores da forma remitenterecorrente da EM 6 .

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“…An area of rapid growth has been the study of enzymes that cleave either proteins or lipids within MS lesions. The work on these proteinases dates back almost 20 years, when they were first demonstrated in CNS of patients with inflammatory demyelinating disease (8). Proteinases are enzymes capable of breaking down peptide bonds.…”

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confidence: 99%

Effectors of Demyelination and Remyelination in the CNS: Implications for Multiple Sclerosis

Rodriguez¹

2007

Brain Pathology

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Most of the research on multiple sclerosis (MS) has focused on the early events that trigger demyelination and subsequent remyelination. Less attention has been given to the factors that directly mediate the demyelination that is the hallmark of the disease. Effector cells or molecules are those factors directly responsible for mediating the damage in the disease. Similarly, there are effector molecules that are critical for remyelination in the central nervous system (CNS). By understanding those effector molecules in demyelination and remyelination that directly influence the pathologic process, we should be able to generate specific therapies with the greatest potential for benefiting MS patients. This review focuses on effector cells and molecules that are critical for demyelination and remyelination in MS but also in experimental models of the disease including experimental autoimmune encephalomyelitis (EAE), virus-induced models of demyelination (Theiler's virus, murine hepatitis virus), and toxic models of demyelination (lysolecithin, ethidium bromide, and cuprizone). These are models in which the effector molecules for demyelination and remyelination have been most precisely evaluated.

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Proteinases in inflammatory demyelinating disease

Cited by 21 publications

References 105 publications

The presence of immunoreactive myelin basic protein peptide in urine of persons with multiple sclerosis

The presence of immunoreactive myelin basic protein peptide in urine of persons with multiple sclerosis

Interferon beta 1-a na esclerose múltipla: experiência de um ano em 62 pacientes

Effectors of Demyelination and Remyelination in the CNS: Implications for Multiple Sclerosis

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