Abstract:
:Neurodegeneration is the main pathological correlate of accumulating disability in progressive stages of Multiple Sclerosis (MS), but both histologic and imaging studies detect significant tissue loss even in early disease. These observations raise the question as to whether neurodegeneration in MS is a primary mechanism or whether it develops secondary to inflammation and demyelination. Recent data suggest that the atrophy of brain and cord is directly linked to inflammation and may partly be independent of demyelination. Released products of both residential and infiltrating immune cells can induce ultrastructural changes and celldeath by multiple mechanism. We propose that the inflammation-induced tissue response is controlled by genetic variations and to some extent involves a mitochondrion-driven mechanism in MS, similar to that described in the final pathway of other neurodegenerative disorders. Current therapeutic strategies primarily target the immune system which results in a successful down-regulation of plaque formation and of relapse rate. However, measures of clinical disability best correlate with the degree of neurodegeneration rather than with the volume of plaques, and these immune-modulating regimens may only incompletely affect the accumulating tissue loss. Considering the need for additional therapeutic strategies, we emphasize the degenerative components, and review a mitochondrial mechanism of tissue loss potentially involved in the process of MS.
journal_name
Neuromolecular Medjournal_title
Neuromolecular medicineauthors
Kalman B,Leist TPdoi
10.1385/NMM:3:3:147keywords:
subject
Has Abstractpub_date
2003-01-01 00:00:00pages
147-58issue
3eissn
1535-1084issn
1559-1174pii
NMM:3:3:147journal_volume
3pub_type
杂志文章,评审abstract::A methylation-based EWAS on carefully phenotyped individuals with Parkinson's disease (PD) was conducted to reveal prioritised genes and pathways with statistically significant and sizable changes in PD and in the anxiety that often accompanies it. This was followed by subsequent replication of top-ranked CpG sites. U...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-014-8332-8
更新日期:2014-12-01 00:00:00
abstract::The metabolic syndrome is characterized by the clustering of various common metabolic abnormalities in an individual and it is associated with increased risk for the development of type 2 diabetes and cardiovascular diseases. Its prevalence in the general population is approximately 25%. Central fat accumulation and i...
journal_title:Neuromolecular medicine
pub_type: 杂志文章,评审
doi:10.1007/s12017-008-8022-5
更新日期:2008-01-01 00:00:00
abstract::Hemorrhagic transformation (HT) of cerebral infarction is a common and serious occurrence following acute ischemic stroke. The expression of survivin, a member of the inhibitor of apoptosis protein family, has been shown to increase after cerebral ischemia. This protein has been mainly located at the microvasculature ...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-014-8333-7
更新日期:2014-12-01 00:00:00
abstract::Classically, histologic grading of gliomas has been used to predict seizure association, with low-grade gliomas associated with an increased incidence of seizures compared to high-grade gliomas. In 2016, WHO reclassified gliomas based on histology and molecular characteristics. We sought to determine whether molecular...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-020-08624-0
更新日期:2020-11-18 00:00:00
abstract::Physical exercise has long been recognized as highly beneficial for brain and body health. The molecular mechanisms responsible for translation of exercise stimuli in the brain have claimed attention due to mounting evidence for the neuroprotective actions of the exercise and its positive effects in preventing both ag...
journal_title:Neuromolecular medicine
pub_type: 杂志文章,评审
doi:10.1007/s12017-008-8026-1
更新日期:2008-01-01 00:00:00
abstract::T-cells directed to self-antigens ("autoimmune" T-cells) have traditionally been perceived as tending to attack the body's own tissues, and likely to exert their destructive effects unless they undergo deletion in the thymus during ontogeny. Naturally occurring CD4+CD25+ regulatory T-cells were viewed as thymus-derive...
journal_title:Neuromolecular medicine
pub_type: 杂志文章,评审
doi:10.1385/NMM:7:3:197
更新日期:2005-01-01 00:00:00
abstract::Selective degeneration and death of motor neurons in SOD1 mutant-mediated amyotrophic lateral sclerosis (ALS) is accompanied by axonal disorganization and reduced slow axonal transport in the three most frequently used mouse models of mutant SOD1-mediated ALS. To test whether suppression of axonal degeneration (freque...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1385/NMM:5:3:193
更新日期:2004-01-01 00:00:00
abstract::The cerebral ischemia is one of the most common diseases in the central nervous system that causes progressive disability or even death. In this connection, the inflammatory response mediated by the activated microglia is believed to play a central role in this pathogenesis. In the event of brain injury, activated mic...
journal_title:Neuromolecular medicine
pub_type: 杂志文章,评审
doi:10.1007/s12017-016-8394-x
更新日期:2016-09-01 00:00:00
abstract::Adenosine A2A receptor (A2AR) is a G-protein-coupled receptor highly expressed in basal ganglia. Its expression levels are severely reduced in Huntington's disease (HD), and several pharmacological therapies have shown its implication in this neurodegenerative disorder. The main goal of this study was to gain insight ...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-013-8219-0
更新日期:2013-06-01 00:00:00
abstract:BACKGROUND:Scutellarin, an herbal compound, can effectively suppress the inflammatory response in activated microglia/brain macrophage(AM/BM) in experimentally induced cerebral ischemia; however, the underlying mechanism for this has not been fully clarified. We sought to elucidate if scutellarin would exert its anti-i...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-019-08582-2
更新日期:2020-06-01 00:00:00
abstract::Cyclin H regulates cell cycle transitions; it always forms trimeric cyclin-dependent protein kinases (CDK)-activating kinase (CAK) complex with CDK7 and MAT1 that phosphorylates a threonine residue in the CDK2 T loop region. However, neither the expression nor function of cyclin H in the central nervous system (CNS) i...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-011-8150-1
更新日期:2011-09-01 00:00:00
abstract::We have previously reported that mild traumatic brain injury (mTBI) induced cognitive deficits as well as apoptotic changes in the brains of mice. Apoptosis may be caused by severe, prolonged accumulation of misfolded proteins, and protein aggregation in the endoplasmic reticulum (ER stress). In an additional study, w...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-015-8340-3
更新日期:2015-03-01 00:00:00
abstract::Cardiovascular diseases including hypertension, myocardial infarction, stroke, and heart failure continue to account for the majority of deaths in the developed world. Whilst the incidence of these clinical disorders does increase with age, outcomes in affected patients tend to be disproportionately adverse with advan...
journal_title:Neuromolecular medicine
pub_type: 杂志文章,评审
doi:10.1007/s12017-008-8034-1
更新日期:2008-01-01 00:00:00
abstract::Reperfusion after cerebral ischemia causes additional ischemic injuries due to sudden recovery of blood supply. It usually produces excessive reactive species, mitochondrial dysfunction, oxidative stress, and cell apoptosis. Our study is designed to examine the role of miR-421 antagomir in cerebral ischemia/reperfusio...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-020-08600-8
更新日期:2020-09-01 00:00:00
abstract::He spent tens of thousands of hours peering through the oculars of a microscope at stained brain tissue sections from thousands of patients who died with or without a neurodegenerative disorder; most of those patients he had himself cared for and had removed and processed their brain tissues upon their death. His disc...
journal_title:Neuromolecular medicine
pub_type: 传,历史文章,杂志文章
doi:10.1007/s12017-010-8124-8
更新日期:2011-03-01 00:00:00
abstract::The high-metabolic demand of neurons and their reliance on glucose as an energy source places them at risk for dysfunction and death under conditions of metabolic and oxidative stress. Uncoupling proteins (UCPs) are mitochondrial inner membrane proteins implicated in the regulation of mitochondrial membrane potential ...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1385/NMM:8:3:389
更新日期:2006-01-01 00:00:00
abstract::Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurodegenerative disorder characterized by progressive cerebellar ataxia and epilepsy. The disease is caused by a pentanucleotide ATTCT expansion in intron 9 of the ATXN10 gene on chromosome 22q13.3. SCA10 has shown a geographical distribution throughout...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-017-8464-8
更新日期:2017-12-01 00:00:00
abstract::Attention deficit hyperactivity disorder (ADHD) is a behavioral diagnosis based on the presence of developmentally inappropriate levels of impulsivity, overactivity, and inattentiveness. It is a familial condition with a complex pattern of inheritance. Variation of several genes involved in the regulation of dopamine,...
journal_title:Neuromolecular medicine
pub_type: 杂志文章,评审
doi:10.1385/NMM:8:4:461
更新日期:2006-01-01 00:00:00
abstract::The gene encoding alpha-T-catenin, CTNNA3, is positioned within a region on chromosome 10, showing strong evidence of linkage to Alzheimer's disease (AD), and is therefore a good positional candidate gene for this disorder. We have demonstrated that alpha-T-catenin is expressed in human brain, and like other alpha-cat...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1385/NMM:5:2:133
更新日期:2004-01-01 00:00:00
abstract::There is increasing evidence implicating apoptosis-mediated cell death in the pathogenesis of neurodegenerative diseases. One important event in the apoptotic cascade is the release of cytochrome c by mitochondria into the cytoplasm, activating caspase-9, leading to the subsequent activation of downstream executioner ...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1385/NMM:1:3:183
更新日期:2002-01-01 00:00:00
abstract::Glioma ranks first among the aggressive brain tumors all over the world. LncRNA LINC00689 has been confirmed to play key roles in the progression of cancers, and LINC00689 was upregulated in glioma. However, the biological function of LINC00689 in glioma is unclear. qRT-PCR was applied to detect the expressions of LIN...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-020-08635-x
更新日期:2021-01-03 00:00:00
abstract::Renalase is a novel, recently identified, flavin adenine dinucleotide-dependent amine oxidase. It is secreted by the kidney and metabolizes circulating catecholamines. Renalase has significant hemodynamic effects, therefore it is likely to participate in the regulation of cardiovascular function.The aim of our study w...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-011-8158-6
更新日期:2011-12-01 00:00:00
abstract::Adiponectin, an adipocytokine released by the adipose tissue and has important roles in the metabolic regulation and inflammatory control, may play an important roles in the physiopathology of psychiatric and neurodegenerative disorders. The aim of the present work was to evaluate adiponectin serum levels in patients ...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-012-8201-2
更新日期:2013-03-01 00:00:00
abstract::Parkinson's disease (PD) features oxidative stress and accumulation of misfolded (unfolded, alternatively folded, or mutant) proteins with associated loss of dopaminergic neurons. Oxidative stress and the accumulated misfolded proteins elicit cellular responses that include an endoplasmic reticulum (ER) stress respons...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-008-8047-9
更新日期:2008-01-01 00:00:00
abstract::Neuronal diseases, including retinal disorders, stroke, Alzheimer's disease, Parkinson's disease and spinal cord injury, affect a large number of people worldwide and cause heavy social and economic burdens. Although many efforts have been made by scientists and clinicians to develop novel drug and healthcare strategi...
journal_title:Neuromolecular medicine
pub_type: 杂志文章,评审
doi:10.1007/s12017-016-8393-y
更新日期:2016-09-01 00:00:00
abstract::Autism spectrum disorder (ASD) is a heterogeneously childhood neurodevelopmental disorder, believed to be under development of various genetic and environmental factors. Autophagy and related pathways have also been implicated in the etiology of ASD. We aimed to investigate autophagic markers by generating the transge...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-019-08579-x
更新日期:2020-06-01 00:00:00
abstract::Phospholipids are the main constituents of brain membranes. Formation of new membranes requires that uridine, the omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA), and choline, the three circulating precursors of major phospholipids, interact via the Kennedy pathway. Supplementation of laboratory...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-016-8414-x
更新日期:2016-09-01 00:00:00
abstract::A number of studies have investigated the association between tumor necrosis factor (TNF)-α gene polymorphisms and ischemic stroke susceptibility. However, results of different individual studies are often inconsistent. To provide a more robust evaluation of the association between polymorphisms of the TNF-α gene and ...
journal_title:Neuromolecular medicine
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s12017-015-8365-7
更新日期:2015-12-01 00:00:00
abstract::Stroke is the second foremost cause of mortality worldwide and a major cause of long-term disability. Due to changes in lifestyle and an aging population, the incidence of stroke continues to increase and stroke mortality predicted to exceed 12 % by the year 2030. However, the development of pharmacological treatments...
journal_title:Neuromolecular medicine
pub_type: 杂志文章,评审
doi:10.1007/s12017-016-8403-0
更新日期:2016-09-01 00:00:00
abstract::Rett syndrome is a severe neurodevelopmental disorder, almost exclusively affecting females and characterized by a wide spectrum of clinical manifestations. Both the classic and atypical forms of Rett syndrome are primarily due to mutations in the methyl-CpG-binding protein 2 (MECP2) gene. Mutations in the X-linked cy...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-012-8212-z
更新日期:2013-03-01 00:00:00