Abstract：
:We have explored the molecular mechanism underlying amyloid beta-peptide (Abeta)-mediated cytotoxicity in vitro. Exposure of murine cerebral endothelial cells (CECs) or C6 glioma cells to Abeta25-35 resulted in dose-dependent cell death. Ceramide is a pro-apoptotic lipid mediator. Forced elevation of cellular ceramide levels, either by application of an exogenous C2 ceramide analogue or bacterial sphingomyelinase that induces endogenous ceramide release from sphingomyelin, mimicked Abeta25-35 cytotoxicity in both CECs and C6 glioma cells. Abeta25-35-induced synthesis of ceramide was selectively mediated by activation of neutral sphingomyelinase (nSMase), but not acidic sphingomyelinase (aSMase) or ceramide synthase. Both 3-O-Me-SM and N-acetyl-L-cysteine, the selective and nonselective pharmacological inhibitors of nSMase, respectively, suppressed nSMase activation, ceramide production, and cytotoxic action induced by Abeta25-35 in CECs. Furthermore, genetic knockdown of nSMase by an antisense strategy rendered C6 glioma cells specifically resistant to Abeta25-35 cytotoxicity without affecting their vulnerability to serum deprivation. Together, nSMase activation with subsequent ceramide production may contribute, at least partially, to Abeta25-35 cytotoxicity in cell types with cerebral endothelial and glial lineage.
journal_name
Neurobiol Disjournal_title
Neurobiology of diseaseauthors
Yang DI,Yeh CH,Chen S,Xu J,Hsu CYdoi
10.1016/j.nbd.2004.06.001keywords:
subject
Has Abstractpub_date
2004-10-01 00:00:00pages
99-107issue
1eissn
0969-9961issn
1095-953Xpii
S0969996104001305journal_volume
17pub_type
杂志文章abstract：:The activation of soluble guanylate cyclase by nitric oxide is increased in the frontal cortex but is reduced in the cerebellum of patients who died with liver cirrhosis. The aims of this work were to assess whether hyperammonemia is responsible for the region-selective alterations in guanylate cyclase modulation in l...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2004.12.001
更新日期：2005-06-01 00:00:00
abstract：:Type 2 diabetes (T2D) is a major risk factor for late-onset Alzheimer's disease (AD). A variety of metabolic changes related to T2D (e.g. hyperinsulinemia, hyperglycemia, and elevated branched-chain amino acids) have been proposed as mechanistic links, but the basis for this association remains unknown. Retromer-depen...
journal_title：Neurobiology of disease
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更新日期：2014-05-01 00:00:00
abstract：:Exaggerated activity in the beta band (13-35 Hz) is a hallmark of basal ganglia signals in patients with Parkinson's disease (PD). Beta activity however is not constantly elevated, but comes in bursts. In previous work we showed that the longer beta bursts are maintained, the more the oscillatory synchronisation withi...
journal_title：Neurobiology of disease
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doi：10.1016/j.nbd.2018.06.007
更新日期：2018-09-01 00:00:00
abstract：:It is well known that the uncoupling between local cerebral glucose utilization (LCGU) and local cerebral blood flow (LCBF), i.e. decrease in LCBF rates with high LCGU, is frequently associated with seizure-induced neuronal damage. This study was performed to assess if the neuroprotective effect of the adenosinergic A...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2010.09.004
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abstract：:Human genetics provides unbiased insights into the causes of human disease, which can be used to create a foundation for effective ways to more accurately diagnose patients, stratify patients for more successful clinical trials, discover and develop new therapies, and ultimately help patients choose the safest and mos...
journal_title：Neurobiology of disease
pub_type： 杂志文章,评审
doi：10.1016/j.nbd.2020.105088
更新日期：2020-12-01 00:00:00
abstract：OBJECTIVE:To investigate structural connectivity and the relationship between axonal microstructure and clinical, cognitive, and motor functions in premanifest (pre-HD) and symptomatic (symp-HD) Huntington's disease. METHOD:Diffusion tensor imaging (DTI) data were acquired from 35 pre-HD, 36 symp-HD, and 35 controls. ...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2014.01.013
更新日期：2014-05-01 00:00:00
abstract：:The terms "neuroacanthocytosis" (NA) and "neurodegeneration with brain iron accumulation" (NBIA) both refer to groups of genetically heterogeneous disorders, classified together due to similarities of their phenotypic or pathological findings. Even collectively, the disorders that comprise these sets are exceedingly r...
journal_title：Neurobiology of disease
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abstract：:Sex differences are a well-known phenomenon in Alzheimer's disease (AD), with women having a higher risk for AD than men. Many AD mouse models display a similar sex-dependent pattern, with females showing earlier cognitive deficits and more severe neuropathology than males. However, whether those differences are relev...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2016.08.009
更新日期：2016-12-01 00:00:00
abstract：:alpha-Synuclein has been identified as a major component of Lewy body inclusions, which are one of the pathologic hallmarks of idiopathic Parkinson's disease. Mutations in alpha-synuclein have been found to be responsible for rare familial cases of Parkinsonism. To test whether overexpression of human alpha-synuclein ...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1006/nbdi.2001.0392
更新日期：2001-06-01 00:00:00
abstract：:Adult-onset hypothyroidism is associated with neurological changes such as cognitive dysfunction and impaired learning, which may be related to alterations of synaptic plasticity. We investigate the consequence of adult-onset hypothyroidism on thyroid-mediated transcription events in striatal synaptic plasticity, and ...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2008.05.015
更新日期：2008-09-01 00:00:00
abstract：:Toll-like receptors (TLRs) are mediators of the innate immune response to exogenous pathogens. They have also been implicated in sterile inflammation associated with systemic injury and non-infectious diseases via binding of endogenous ligands, possibly released by damaged cells. Emerging evidence indicates that some ...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2012.12.012
更新日期：2013-06-01 00:00:00
abstract：:Previous studies have indicated that administration of glial cell line-derived neurotrophic factor (GDNF) counteracts neuronal death after stroke. However, in these studies damage was evaluated at most a few days after the insult. Here, we have explored the long-term consequences of two routes of GDNF delivery to the ...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2003.08.002
更新日期：2003-12-01 00:00:00
abstract：:Charcot-Marie-Tooth disease (CMT) is a genetic disorder that can be caused by aberrations in >80 genes. CMT has heterogeneous modes of inheritance, including autosomal dominant, autosomal recessive, X-linked dominant, and X-linked recessive. Over 95% of cases are dominantly inherited. In this study, we investigated wh...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2017.01.006
更新日期：2017-04-01 00:00:00
abstract：:The neuropathology of hippocampal seizure foci in human temporal lobe epilepsy (TLE) and several animal models of epilepsy reveal extensive neuronal loss along with astrocyte and microglial activation. Studies of these models have advanced hypotheses that propose both pathological changes are essential for seizure gen...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2020.105152
更新日期：2021-01-01 00:00:00
abstract：:Cellular mechanisms play a role in conversion of the normal prion protein PrP(C) to the disease-associated protein PrP(Sc). The cells provide not only PrP(C), but also still largely undefined factors required for efficient prion replication. Previously, we have observed that interference with ERK and p38-JNK MAP kinas...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2013.05.014
更新日期：2013-10-01 00:00:00
abstract：:Charcot-Marie-Tooth disease type 2B (CMT2B) is an inherited axonal peripheral neuropathy. It is characterised by prominent sensory loss, often complicated by severe ulcero-mutilations of toes or feet, and variable motor involvement. Missense mutations in RAB7A, the gene encoding the small GTPase Rab7, cause CMT2B and ...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2014.01.021
更新日期：2014-05-01 00:00:00
abstract：:Background While significant advances have been made in uncovering the aetiology of Alzheimer's disease and related dementias at the genetic level, molecular events at the epigenetic level remain largely undefined. Emerging evidence indicates that small non-coding RNAs (sncRNAs) and their associated RNA modifications ...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2020.105058
更新日期：2020-11-01 00:00:00
abstract：:We determined whether the preferential toxicity of tetrahydrobiopterin (BH4) on dopamine-producing cells, which we have previously observed in vitro, might also occur in vivo and generate characteristics associated with Parkinson's disease. Intrastriatal BH4 injection caused a loss of tyrosine hydroxylase immunoreacti...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/s0969-9961(03)00037-8
更新日期：2003-07-01 00:00:00
abstract：:The identification of novel molecular targets crucially involved in motor neuron degeneration/survival is a necessary step for the development of hopefully more effective therapeutic strategies for amyotrophic lateral sclerosis (ALS) patients. In this view, S1R, an endoplasmic reticulum (ER)-resident receptor with cha...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2013.10.010
更新日期：2014-02-01 00:00:00
abstract：:Neuropeptide Y (NPY) is an important 36 amino acid peptide that is abundantly expressed in the mammalian CNS and is known to be an endogenous modulator of seizure activity, including in rat models of Genetic Generalised Epilepsy (GGE) with absence seizures. Studies have shown that viral-mediated "gene therapy" with ov...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2018.01.016
更新日期：2018-05-01 00:00:00
abstract：:Spinal cord injury (SCI) is a major cause of disability, and at present, there is no universally accepted treatment. The functional decline following SCI is contributed to both direct mechanical injury and secondary pathophysiological mechanisms that are induced by the initial trauma. These mechanisms initially involv...
journal_title：Neurobiology of disease
pub_type： 杂志文章,评审
doi：10.1016/j.nbd.2003.11.015
更新日期：2004-04-01 00:00:00
abstract：:Neural stem cells (NSCs) are multipotent, self-renewing progenitors that generate progeny that differentiate into neurons and glia. NSCs in the adult mammalian brain are generally quiescent. Environmental stimuli such as learning or exercise can activate quiescent NSCs, inducing them to proliferate and produce new neu...
journal_title：Neurobiology of disease
pub_type： 杂志文章,评审
doi：10.1016/j.nbd.2017.01.010
更新日期：2017-11-01 00:00:00
abstract：:Nicotinamide adenine dinucleotide phosphate oxidase (NOX) is widely expressed in brain tissue including neurons, glia, and endothelia in neurovascular units. It is a major source of oxidants in the post-ischemic brain and significantly contributes to ischemic brain damage. Inflammation occurs after brain ischemia and ...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2011.01.027
更新日期：2011-06-01 00:00:00
abstract：:Glutamate-induced delayed calcium dysregulation (DCD) is a causal factor leading to neuronal death. The mechanism of DCD is not clear but Ca2+ influx via N-methyl-d-aspartate receptors (NMDAR) and/or the reverse plasmalemmal Na+/Ca2+ exchanger (NCXrev) could be involved in DCD. However, the extent to which NMDAR and N...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2011.12.051
更新日期：2012-04-01 00:00:00
abstract：:Neurofibrillary degeneration in transgenic models of tauopathies has been observed to be enhanced when these models are crossed with transgenic models developing an Aβ pathology. The mechanisms leading to this enhanced tau pathology are not well understood. We have performed a detailed analysis of tau misprocessing in...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2013.09.010
更新日期：2014-02-01 00:00:00
abstract：:Extracellular nucleotides exert a variety of biological actions through different subtypes of P2 receptors. Here we characterized in the human neuroblastoma SH-SY5Y cells the simultaneous presence of various P2 receptors, belonging to the P2X ionotropic and P2Y metabotropic families. Western blot analysis detected the...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2004.09.001
更新日期：2005-02-01 00:00:00
abstract：:The role of endothelial nitric oxide (NO) in the cerebrovascular response to partial seizures was investigated in mice deleted for the endothelial NO synthase gene (eNOS-/-) and in their paired wild-type (WT) congeners. Local cerebral blood flow (LCBF, quantitative [14C]iodoantipyrine method) was measured 3-6 h after ...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2006.03.002
更新日期：2006-07-01 00:00:00
abstract：:In addition to the substantial biological diversity among humans, our limited ability to reliably measure expression changes of small magnitude significantly reduces our capacity to obtain convergent sets of transcriptome data in postmortem brain. In particular, differences in the structure and sensitivity/reproducibi...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2004.10.020
更新日期：2005-04-01 00:00:00
abstract：:In multiple sclerosis (MS), post-mortem studies of human brain tissue as well as data from animal models have shown that apoptosis of neurons occurs to a significant extent during this disease. As neurodegeneration in MS correlates with permanent neurological deficits in patients, understanding the mechanisms would be...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2005.03.003
更新日期：2005-11-01 00:00:00
abstract：:In this review, we describe insights into beta-amyloid (Abeta) production using aged dogs as a model of human brain aging. The advantage of using dogs is that they naturally accumulate Abeta neuropathology with age. In parallel, dogs also develop age-associated learning and memory impairments. Thus, dogs can complemen...
journal_title：Neurobiology of disease
pub_type： 杂志文章,评审
doi：10.1006/nbdi.2002.0476
更新日期：2002-02-01 00:00:00
