Glatiramer acetate induces pro-apoptotic mechanisms involving Bcl-2, Bax and Cyt-c in peripheral lymphocytes from multiple sclerosis patients.

Abstract:

:Apoptotic deletion of autoreactive T-cells is defective in patients with multiple sclerosis (MS). Glatiramer acetate (GA) treatment seems to restore apoptosis of detrimental T-cells. We analyzed the mitochondria membrane pro- (Bax) and anti-apoptotic (Bcl- 2) and cytosolic pro-apoptotic (Cyt-c, APAF-1) proteins expression in peripheral lymphocytes from relapsing-remitting (RR) MS patients during GA treatment. Blood samples were collected from 8 healthy controls (HCs) and from 8 RR MS patients prior to and every three months during the 9 months of GA treatment. Peripheral blood mononuclear cells (PBMNCs) Bcl-2, Bax, Cyt-c and APAF-1 were quantified by western blot followed by densitometric scanning and Bax/Bcl-2, cytosolic Cyt-c/Bcl-2 and APAF-1/Bcl-2 ratios were calculated. T-cells were in vitro tested for oxygen consumption by a respirometric analysis. Bax/Bcl-2, cytosolic Cyt-c/Bcl-2 and APAF-1/Bcl-2 ratios in untreated MS patients were significantly (p < 0.05) lower than in HCs. Bax/Bcl-2 ratio increased (p = 0.03) and Cyt-c/Bcl-2 ratio showed a trend to increase during the 9 months of GA treatment in MS patients. A reduction of 58% and 59% in oxygen consumption by PBMNCs was evident after GA treatment in vitro or when GA treated patients' cells were compared with those from HCs, respectively. Our findings suggest that GA exerts a regulatory effect on peripheral T lymphocytes through pro-apoptosis mechanisms involving mitochondria and cytosolic proteins.

journal_name

J Neurol

journal_title

Journal of neurology

authors

Ruggieri M,Avolio C,Scacco S,Pica C,Lia A,Zimatore GB,Papa S,Livrea P,Trojano M

doi

10.1007/s00415-005-0965-y

keywords:

subject

Has Abstract

pub_date

2006-02-01 00:00:00

pages

231-6

issue

2

eissn

0340-5354

issn

1432-1459

journal_volume

253

pub_type

杂志文章
  • Vertebral artery stenosis in the Basilar Artery International Cooperation Study (BASICS): prevalence and outcome.

    abstract::We assessed the prevalence of vertebral artery (VA) stenosis or occlusion and its influence on outcome in patients with acute basilar artery occlusion (BAO). We studied 141 patients with acute BAO enrolled in the Basilar Artery International Cooperation Study (BASICS) registry of whom baseline CT angiography (CTA) of ...

    journal_title:Journal of neurology

    pub_type: 杂志文章

    doi:10.1007/s00415-014-7583-5

    authors: Compter A,van der Hoeven EJ,van der Worp HB,Vos JA,Weimar C,Rueckert CM,Kappelle LJ,Algra A,Schonewille WJ,BASICS Study Group.

    更新日期:2015-02-01 00:00:00

  • Differences in treatment of anti-NMDA receptor encephalitis: results of a worldwide survey.

    abstract::The objective of the study was to identify differences in treatment strategies for anti-NMDA receptor encephalitis based on specialty of treating physicians, geographic location, and years in practice. We conducted an anonymous worldwide electronic survey through the Practice Current section of Neurology® Clinical Pra...

    journal_title:Journal of neurology

    pub_type: 杂志文章

    doi:10.1007/s00415-017-8407-1

    authors: Bartolini L,Muscal E

    更新日期:2017-04-01 00:00:00

  • Normalized grip strength is a sensitive outcome measure through all stages of Duchenne muscular dystrophy.

    abstract:OBJECTIVE:The main aim was to explore the changes in hand-grip strength in patients with Duchenne muscular dystrophy (DMD) aged 5-29 years. Secondary aims were to test the effect of mutation, ambulatory status and glucocorticoid use on grip strength and its changes over time and to compute the number of subjects needed...

    journal_title:Journal of neurology

    pub_type: 杂志文章

    doi:10.1007/s00415-020-09800-9

    authors: Hogrel JY,Decostre V,Ledoux I,de Antonio M,Niks EH,de Groot I,Straub V,Muntoni F,Ricotti V,Voit T,Seferian A,Gidaro T,Servais L

    更新日期:2020-07-01 00:00:00

  • Macro EMG follow-up study in post-poliomyelitis patients.

    abstract::We investigated the muscle strength and motor unit (MU) territory of five patients with postpolio syndrome (PPS), six stable patients with prior poliomyelitis, and five healthy volunteers. The MU territory was assessed by measuring amplitudes of motor unit potentials (MUPs) recorded by the macro EMG technique. The inv...

    journal_title:Journal of neurology

    pub_type: 杂志文章

    doi:10.1007/BF00920572

    authors: Ivanyi B,Ongerboer de Visser BW,Nelemans PJ,de Visser M

    更新日期:1994-12-01 00:00:00

  • Changes of circadian blood pressure patterns and cardiovascular parameters indicate lateralization of sympathetic activation following hemispheric brain infarction.

    abstract::The effects of left- and right-sided hemispheric brain infarction on variability in circadian blood pressure and cardiovascular measures were investigated in 35 patients to test for asymmetry of the sympathetic consequences of stroke. No significant differences regarding age, size of infarction or extent and frequency...

    journal_title:Journal of neurology

    pub_type: 杂志文章

    doi:10.1007/BF00878874

    authors: Sander D,Klingelhöfer J

    更新日期:1995-05-01 00:00:00

  • Step length predicts executive dysfunction in Parkinson's disease: a 3-year prospective study.

    abstract::Cognition and gait appear to be closely related. The chronological interplay between cognitive decline and gait dysfunction is not fully understood. The aim of the present prospective study is investigating whether the dysfunction of specific gait parameters, during specific task and medication conditions, may predict...

    journal_title:Journal of neurology

    pub_type: 杂志文章

    doi:10.1007/s00415-018-8973-x

    authors: Amboni M,Iuppariello L,Iavarone A,Fasano A,Palladino R,Rucco R,Picillo M,Lista I,Varriale P,Vitale C,Cesarelli M,Sorrentino G,Barone P

    更新日期:2018-10-01 00:00:00

  • Cognitive phenotypes in multiple sclerosis.

    abstract:BACKGROUND:Cognitive impairment is a debilitating symptom experienced by ~ 50% of multiple sclerosis patients, with processing speed (PS) and memory most affected. Until now, the field has considered cognition in a binary fashion: patients are designated as impaired or not impaired. This designation is typically arrive...

    journal_title:Journal of neurology

    pub_type: 杂志文章

    doi:10.1007/s00415-018-8747-5

    authors: Leavitt VM,Tosto G,Riley CS

    更新日期:2018-03-01 00:00:00

  • Acetylcholine-receptor-like protein from human thymoma associated with myasthenia gravis.

    abstract::Cobrotoxin-binding protein was isolated by affinity chromatography from human thymoma which had been surgically removed from patients with myasthenia gravis. The protein was composed of polypeptides with a molecular mass of 40, 51, 65, and 74 kilodaltons as determined by polyacrylamide gel electrophoresis in the prese...

    journal_title:Journal of neurology

    pub_type: 杂志文章

    doi:10.1007/BF00618251

    authors: Kawanami S,Kamei H,Oita J,Kurokawa M,Uchida Y,Hayashi K

    更新日期:1987-05-01 00:00:00

  • Progressive myoclonus epilepsy in Down syndrome patients with dementia.

    abstract::This study aimed to elucidate the natural history of senile myoclonic epilepsy, a type of myoclonic epilepsy associated with Alzheimer's disease in adult Down syndrome patients. Twelve Down syndrome patients over the age of 40 years with myoclonic epilepsy and Alzheimer's disease underwent clinical, neuropsychological...

    journal_title:Journal of neurology

    pub_type: 杂志文章

    doi:10.1007/s00415-014-7376-x

    authors: d'Orsi G,Specchio LM,Apulian Study Group on Senile Myoclonic Epilepsy.

    更新日期:2014-08-01 00:00:00

  • Acanthocytosis and neurological disorders.

    abstract::Acanthocytosis occurs because of ultrastructural abnormalities of the erythrocyte membranous skeleton resulting in reduced membrane fluidity. At least three hereditary neurological conditions are associated with it, although as yet the pathogenesis of the neurological features is unknown. In abetalipoproteinaemia, an ...

    journal_title:Journal of neurology

    pub_type: 杂志文章,评审

    doi:10.1007/s004150170241

    authors: Stevenson VL,Hardie RJ

    更新日期:2001-02-01 00:00:00

  • Longitudinal cognitive and functional changes in primary progressive aphasia.

    abstract:OBJECTIVE:The variants of primary progressive aphasia (PPA) are predominantly diagnosed on the basis of specific profiles of language impairments. Deficits in other cognitive domains and their evolution over time are less well documented. This study examined the cognitive profiles of the PPA variants over time and dete...

    journal_title:Journal of neurology

    pub_type: 杂志文章

    doi:10.1007/s00415-020-10382-9

    authors: Foxe D,Irish M,Hu A,Carrick J,Hodges JR,Ahmed RM,Burrell JR,Piguet O

    更新日期:2021-01-08 00:00:00

  • The epidemiology of neuromyelitis optica amongst adults in the Merseyside county of United Kingdom.

    abstract::Neuromyelitis optica (NMO) is an uncommon, demyelinating disease that causes long-term disability in adults. Though much has recently been learned about its pathogenesis, there are still only a few studies regarding the epidemiology of NMO. The aim of the study was to describe the epidemiology of NMO among adults in t...

    journal_title:Journal of neurology

    pub_type: 杂志文章

    doi:10.1007/s00415-013-6926-y

    authors: Jacob A,Panicker J,Lythgoe D,Elsone L,Mutch K,Wilson M,Das K,Boggild M

    更新日期:2013-08-01 00:00:00

  • Periodic limb movements during sleep are a frequent finding in patients with Gilles de la Tourette's syndrome.

    abstract::Gilles de la Tourette's syndrome (GTS) and restless legs syndrome (RLS) are two different neurological disorders with common features such as involuntary movements. In both disorders a disturbance of the dopaminergic system has been considered among other possible mechanisms. Since periodic leg movements (PLMS) during...

    journal_title:Journal of neurology

    pub_type: 杂志文章

    doi:10.1007/s004150050136

    authors: Voderholzer U,Müller N,Haag C,Riemann D,Straube A

    更新日期:1997-08-01 00:00:00

  • MRI findings of small subcortical "lacunar-like" infarction resulting from large vessel disease.

    abstract::Small subcortical infarctions resulting from large-vessel disease are often observed. It is important to distinguish these from pure lacunar infarction resulting from small-vessel disease because the investigations and examinations differ. We investigated the differences on brain magnetic resonance imaging (MRI) betwe...

    journal_title:Journal of neurology

    pub_type: 杂志文章

    doi:10.1007/s004150050584

    authors: Adachi T,Kobayashi S,Yamaguchi S,Okada K

    更新日期:2000-04-01 00:00:00

  • Association between Synapsin III gene promoter polymorphisms and multiple sclerosis.

    abstract::Although multiple sclerosis (MS) is considered to be an inflammatory demyelinating disease, increasing evidence indicates that it is also an axonal pathology; indeed, studies of experimental allergic encephalitis showed that several neuronal proteins such as synapsins take part in the pathogenesis of the axonal dysfun...

    journal_title:Journal of neurology

    pub_type: 杂志文章

    doi:10.1007/s00415-004-0293-7

    authors: Liguori M,Cittadella R,Manna I,Valentino P,La Russa A,Serra P,Trojano M,Messina D,Ruscica F,Andreoli V,Romeo N,Livrea P,Quattrone A

    更新日期:2004-02-01 00:00:00

  • Euro-Esli: a European audit of real-world use of eslicarbazepine acetate as a treatment for partial-onset seizures.

    abstract::The Euro-Esli study was an exploratory pooled analysis of data from 14 European clinical practice studies, which was conducted to audit the real-world effectiveness, safety, and tolerability of eslicarbazepine acetate (ESL) as an adjunctive treatment for partial-onset seizures. Retention and effectiveness were assesse...

    journal_title:Journal of neurology

    pub_type: 杂志文章,多中心研究

    doi:10.1007/s00415-017-8618-5

    authors: Villanueva V,Holtkamp M,Delanty N,Rodriguez-Uranga J,McMurray R,Santagueda P

    更新日期:2017-11-01 00:00:00

  • Post-stroke emotional incontinence after small lenticulocapsular stroke: correlation with lesion location.

    abstract::Although post-stroke emotional incontinence (EI) often occurs after lenticulocapsular strokes, what factors determine the development of EI in these patients has not been identified. I prospectively studied the development of EI in 25 patients (13 men and 12 women, mean age 58.5 years) with single, unilateral, first-e...

    journal_title:Journal of neurology

    pub_type: 杂志文章

    doi:10.1007/s00415-002-0714-4

    authors: Kim JS

    更新日期:2002-07-01 00:00:00

  • POLR3A-related spastic ataxia: new mutations and a look into the phenotype.

    abstract::Adolescent-onset spastic ataxia is a proposed novel phenotype in compound heterozygous carriers of an intronic mutation (c.1909 + 22G > A) in the POLR3A gene. Here, we present ten new cases of POLR3A-related spastic ataxia and discuss the genetic, clinical and imaging findings. Patients belonged to six pedigrees with ...

    journal_title:Journal of neurology

    pub_type: 杂志文章

    doi:10.1007/s00415-019-09574-9

    authors: Infante J,Serrano-Cárdenas KM,Corral-Juan M,Farré X,Sánchez I,de Lucas EM,García A,Martín-Gurpegui JL,Berciano J,Matilla-Dueñas A

    更新日期:2020-02-01 00:00:00

  • An update on MSA: premotor and non-motor features open a window of opportunities for early diagnosis and intervention.

    abstract::In this review, we describe the wide clinical spectrum of features that can be seen in multiple system atrophy (MSA) with a focus on the premotor phase and the non-motor symptoms providing an up-to-date overview of the current understanding in this fast-growing field. First, we highlight the non-motor features at dise...

    journal_title:Journal of neurology

    pub_type: 杂志文章

    doi:10.1007/s00415-020-09881-6

    authors: Chelban V,Catereniuc D,Aftene D,Gasnas A,Vichayanrat E,Iodice V,Groppa S,Houlden H

    更新日期:2020-09-01 00:00:00

  • T2*-weighted MRI in diagnosis of multiple system atrophy. A practical approach for clinicians.

    abstract:BACKGROUND:Putaminal iron deposition is a histopathological feature of multiple system atrophy (MSA), which is not observed in patients with idiopathic Parkinson's disease (PD). T2*-weighted magnetic resonance imaging (MRI) gradient echo (GE) sequences are sensitive for paramagnetic susceptibility changes and therefore...

    journal_title:Journal of neurology

    pub_type: 杂志文章

    doi:10.1007/s00415-006-0496-1

    authors: von Lewinski F,Werner C,Jörn T,Mohr A,Sixel-Döring F,Trenkwalder C

    更新日期:2007-09-01 00:00:00

  • Female carriers of X-chromosomal adrenoleukodystrophy: a major differential diagnosis in progressive myelopathy.

    abstract::Adrenoleukodystrophy (ALD) and adrenomyeloneuropathy (AMN) are allelic X-chromosomal disorders of peroxisomal lipid metabolism due to mutations of the ABCD1-gene, leading, respectively, to leukoencephalopathy or myeloneuropathy in male patients. We report a family with two symptomatic carriers in subsequent generation...

    journal_title:Journal of neurology

    pub_type: 信件

    doi:10.1007/s00415-010-5505-8

    authors: Guettsches AK,Kuechler A,Gal A,Schmitz W,Tegenthoff M,Vorgerd M

    更新日期:2010-08-01 00:00:00

  • PRRT2-related disorders: further PKD and ICCA cases and review of the literature.

    abstract::Recent studies reported mutations in the gene encoding the proline-rich transmembrane protein 2 (PRRT2) to be causative for paroxysmal kinesigenic dyskinesia (PKD), PKD combined with infantile seizures (ICCA), and benign familial infantile seizures (BFIS). PRRT2 is a presynaptic protein which seems to play an importan...

    journal_title:Journal of neurology

    pub_type: 杂志文章,评审

    doi:10.1007/s00415-012-6777-y

    authors: Becker F,Schubert J,Striano P,Anttonen AK,Liukkonen E,Gaily E,Gerloff C,Müller S,Heußinger N,Kellinghaus C,Robbiano A,Polvi A,Zittel S,von Oertzen TJ,Rostasy K,Schöls L,Warner T,Münchau A,Lehesjoki AE,Zara F,Lerch

    更新日期:2013-05-01 00:00:00

  • Progress in Huntington's disease: the search for markers of disease onset and progression.

    abstract::Unlike most neurodegenerative disorders, individuals at risk from Huntington's disease can be identified prior to the onset of clinical signs of the disease by virtue of it being an autosomal dominant condition. This provides the hypothetical opportunity to delay disease onset and/or slow down the progression of the d...

    journal_title:Journal of neurology

    pub_type: 杂志文章,评审

    doi:10.1007/s00415-015-7700-0

    authors: Mason S,Barker RA

    更新日期:2015-08-01 00:00:00

  • Sexuality in patients with amyotrophic lateral sclerosis and their partners.

    abstract::Sexuality in patients with amyotrophic lateral sclerosis (ALS) has received little attention so far. Although sexual function is not directly affected by the disease process, several patients have reported problems within their sexual relationship. We performed a questionnaire survey to ascertain the extent and clinic...

    journal_title:Journal of neurology

    pub_type: 杂志文章

    doi:10.1007/s00415-004-0351-1

    authors: Wasner M,Bold U,Vollmer TC,Borasio GD

    更新日期:2004-04-01 00:00:00

  • Artistic occupations are associated with a reduced risk of Parkinson's disease.

    abstract::Parkinson's disease (PD) is preceded by a premotor phase of unknown duration. Dopaminergic degeneration during this phase may lead to subtle cognitive and behavioural changes, such as decreased novelty seeking. Consequently, premotor subjects might be most comfortable in jobs that do not require optimal dopamine level...

    journal_title:Journal of neurology

    pub_type: 杂志文章

    doi:10.1007/s00415-015-7828-y

    authors: Haaxma CA,Borm GF,van der Linden D,Kappelle AC,Bloem BR

    更新日期:2015-09-01 00:00:00

  • Cerebral ischaemia produced by homologous blood clot emboli in rabbit.

    abstract::In 40 rabbits cerebral ischaemia was induced by autologous blood clot emboli injected into the middle cerebral artery. Autologous blood clot formed spontaneously (within 2 h) in a catheter fixed in the internal carotid artery. The effects of embolization were investigated on arterial blood pressure, respiration, local...

    journal_title:Journal of neurology

    pub_type: 杂志文章

    doi:10.1007/BF00314181

    authors: Fekete I,Hegedüs K,Molnár L

    更新日期:1988-05-01 00:00:00

  • The importance of maintaining effective therapy in multiple sclerosis.

    abstract::The INCOMIN study (INdependent COMparison of INterferons) lends further support to the growing body of evidence that both dose and frequency of interferon beta (IFNbeta) administration are important in the treatment of multiple sclerosis (MS). High-dose, high-frequency IFNbeta (IFNbeta-1b 250 microg eod sc and IFNbeta...

    journal_title:Journal of neurology

    pub_type: 杂志文章,评审

    doi:10.1007/s00415-005-2016-0

    authors: Durelli L,Clerico M

    更新日期:2005-09-01 00:00:00

  • The first Italian family with tibial muscular dystrophy caused by a novel titin mutation.

    abstract::Tibial muscular dystrophy (TMD) or Udd myopathy is an autosomal dominant distal myopathy with late onset, at first described in the Finnish population. We report here the first Italian cases of TTN mutated titinopathy. The proband, a 60 year-old female, had the first muscular signs at the age of 59 years, with difficu...

    journal_title:Journal of neurology

    pub_type: 杂志文章

    doi:10.1007/s00415-009-5372-3

    authors: Pollazzon M,Suominen T,Penttilä S,Malandrini A,Carluccio MA,Mondelli M,Marozza A,Federico A,Renieri A,Hackman P,Dotti MT,Udd B

    更新日期:2010-04-01 00:00:00

  • L-2-hydroxyglutaric aciduria: two Japanese adult cases in one family.

    abstract::We report two adult Japanese sisters with L-2-hydroxy-glutaric aciduria (acidemia), both of whom were much older (aged 57, 47 years old) than previously reported patients (from neonate to 44 years old), and who presented with differing severity. Magnetic resonance imaging revealed typical subcortical white matter lesi...

    journal_title:Journal of neurology

    pub_type: 杂志文章

    doi:10.1007/s004150050367

    authors: Fujitake J,Ishikawa Y,Fujii H,Nishimura K,Hayakawa K,Inoue F,Terada N,Okochi M,Tatsuoka Y

    更新日期:1999-05-01 00:00:00

  • Non-CNS pathogenic origin of Parkinson's disease.

    abstract::The gut with its variety of microbiota may serve as an etiological origin of diseases. Gut microbes may also play a role in the pathogenesis of diseases beyond their simple nutritional maintenance and support. For example, gut protein aggregation, possibly aided by microbes as well as nasal influences, might be linked...

    journal_title:Journal of neurology

    pub_type: 杂志文章

    doi:10.1007/s00415-017-8588-7

    authors: Choudhry H,Perlmuter LC

    更新日期:2017-09-01 00:00:00