Abstract:
:Lipid metabolism is drastically dysregulated in amyotrophic lateral sclerosis and impacts prognosis of patients. Animal models recapitulate alterations in the energy metabolism, including hypermetabolism and severe loss of adipose tissue. To gain insight into the molecular mechanisms underlying disease progression in amyotrophic lateral sclerosis, we have performed RNA-sequencing and lipidomic profiling in spinal cord of symptomatic SOD1G86R mice. Spinal transcriptome of SOD1G86R mice was characterized by differential expression of genes related to immune system, extracellular exosome, and lysosome. Hypothesis-driven identification of metabolites showed that lipids, including sphingomyelin(d18:0/26:1), ceramide(d18:1/22:0), and phosphatidylcholine(o-22:1/20:4) showed profound altered levels. A correlation between disease severity and gene expression or metabolite levels was found for sphingosine, ceramide(d18:1/26:0), Sgpp2, Sphk1, and Ugt8a. Joint-analysis revealed a significant enrichment of glycosphingolipid metabolism in SOD1G86R mice, due to the down-regulation of ceramide, glucosylceramide, and lactosylceramide and the overexpression of genes involved in their recycling in the lysosome. A drug-gene interaction database was interrogated to identify potential drugs able to modulate the dysregulated genes from the signaling pathway. Our results suggest that complex lipids are pivotally changed during the first phase of motor symptoms in an animal model of amyotrophic lateral sclerosis.
journal_name
Front Mol Neuroscijournal_title
Frontiers in molecular neuroscienceauthors
Henriques A,Croixmarie V,Bouscary A,Mosbach A,Keime C,Boursier-Neyret C,Walter B,Spedding M,Loeffler JPdoi
10.3389/fnmol.2017.00433subject
Has Abstractpub_date
2018-01-04 00:00:00pages
433issn
1662-5099journal_volume
10pub_type
杂志文章abstract::Stroke results in high morbidity and high mortality worldwide, with ischemic stroke accounting for 80% to 85%. As effective treatments for ischemic stroke remain limited because of the narrow therapeutic time window, a better understanding of the pathologic mechanism and new therapeutic intervention targets are needed...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2019.00061
更新日期:2019-03-22 00:00:00
abstract::Alzheimer's disease (AD) is the most common cause of dementia and is characterized by the buildup of β-amyloid plaques and neurofibrillary Tau tangles. This leads to decreased synaptic efficacy, cell death, and, consequently, brain atrophy in patients. Behaviorally, this manifests as memory loss and confusion. Using a...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2020.594319
更新日期:2020-11-16 00:00:00
abstract::[This corrects the article DOI: 10.3389/fnmol.2019.00099.]. ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,已发布勘误
doi:10.3389/fnmol.2019.00149
更新日期:2019-06-12 00:00:00
abstract::Cleavage of the amyloid precursor protein (APP) by α-secretase generates an extracellularly released fragment termed secreted APP-alpha (APPsα). Not only is this process of interest due to the cleavage of APP within the amyloid-beta sequence, but APPsα itself has many physiological properties that suggest its great po...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2017.00030
更新日期:2017-02-07 00:00:00
abstract::N-methyl-d-aspartate receptors (NMDARs) play an important role in many aspects of nervous system function such as synaptic plasticity and neuronal development. NMDARs are heteromers consisting of an obligate NR1 and most commonly one or two kinds of NR2 subunits. While the receptors have been well characterized in som...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/neuro.02.004.2009
更新日期:2009-09-11 00:00:00
abstract::Neuroimaging studies have demonstrated that irritable bowel syndrome (IBS)-a relapsing functional bowel disorder-presents with disrupted brain connections. However, little is known about the alterations of interhemispheric functional connectivity and underlying structural connectivity in IBS. This study combined resti...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2016.00141
更新日期:2016-12-06 00:00:00
abstract::The degeneration of dopaminergic neurons during Parkinson's disease (PD) is intimately linked to malfunction of α-synuclein (αSyn), the main component of the proteinaceous intracellular inclusions characteristic for this pathology. The cytotoxicity of αSyn has been attributed to disturbances in several biological proc...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2017.00207
更新日期:2017-06-30 00:00:00
abstract::Membrane bound guanylate cyclases are expressed in rod and cone cells of the vertebrate retina and mutations in several domains of rod outer segment guanylate cyclase 1 (ROS-GC1 encoded by the gene GUCY2D) correlate with different forms of retinal degenerations. In the present work we investigated the biochemical cons...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2014.00004
更新日期:2014-02-26 00:00:00
abstract::The neuromuscular junction (NMJ) is the chemical synapse connecting motor neurons and skeletal muscle fibers. NMJs allow all voluntary movements, and ensure vital functions like breathing. Changes in the structure and function of NMJs are hallmarks of numerous pathological conditions that affect muscle function includ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2020.00162
更新日期:2020-08-28 00:00:00
abstract::Neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and spinal muscular atrophy (SMA) are chronic, progressive, and age-associated neurological disorders characterized by neuronal deterioration in specific brain regions. Although the specific path...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2019.00141
更新日期:2019-06-05 00:00:00
abstract::In recent years, signaling through ubiquitin has been shown to be of great importance for normal brain development. Indeed, fluctuations in ubiquitin levels and spontaneous mutations in (de)ubiquitination enzymes greatly perturb synapse formation and neuronal transmission. In the brain, expression of lysine (K) 48-lin...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2016.00043
更新日期:2016-06-10 00:00:00
abstract::Peroxisome proliferator activated receptors (PPARs) are nuclear hormone receptors that act as transcription factors in response to endogenous lipid messengers. The fibrates and thiazolidinediones are synthetic PPAR agonists used clinically to treat dyslipidemia and Type 2 Diabetes Mellitus, respectively, but also impr...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2018.00331
更新日期:2018-09-19 00:00:00
abstract::The constitutively active protein glycogen synthase kinase 3 (GSK3), a serine/threonine kinase, acts paradoxically as a tumor suppressor in some cancers while potentiates growth in others. Deciphering what governs its actions is vital for understanding many pathological conditions, including brain cancer. What are see...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2011.00047
更新日期:2011-11-25 00:00:00
abstract::Background: An imbalance between total training load and total recovery may cause overtraining (OT). The purpose of the present study was to verify the effects of OT on the expression of brain-derived neurotrophic factor (BDNF), its receptor tropomyosin receptor kinase B (TrkB) and p75 and the dynamic expression patte...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2020.00007
更新日期:2020-01-30 00:00:00
abstract::Control of proper protein synthesis, function, and turnover is essential for the health of all cells. In neurons these demands take on the additional importance of supporting and regulating the highly dynamic connections between neurons that are necessary for cognitive function, learning, and memory. Regulating multip...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2014.00063
更新日期:2014-07-08 00:00:00
abstract::Inflammation contributes to cognitive impairment in patients with hepatic encephalopathy (HE). However, the process by which peripheral inflammation results in cognitive impairment remains unclear. In animal models, neuroinflammation and altered neurotransmission mediate cognitive impairment. Taking into account these...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2016.00106
更新日期:2016-11-02 00:00:00
abstract::Alzheimer's disease (AD) is the most common type of senile dementia, characterized by neurofibrillary tangle and amyloid plaque in brain pathology. Major efforts in AD drug were devoted to the interference with the production and accumulation of amyloid-β peptide (Aβ), which plays a causal role in the pathogenesis of ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2020.00137
更新日期:2020-08-04 00:00:00
abstract::Panx1 forms plasma membrane channels in brain and several other organs, including the inner ear. Biophysical properties, activation mechanisms and modulators of Panx1 channels have been characterized in detail, however the impact of Panx1 on auditory function is unclear due to conflicts in published results. To addres...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2017.00379
更新日期:2017-11-28 00:00:00
abstract::Background: Galectins, a family of non-classically secreted, β-galactoside binding proteins is involved in several brain disorders; however, no systematic knowledge on the normal neuroanatomical distribution and functions of galectins exits. Hence, the major purpose of this study was to understand spatial distribution...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2016.00139
更新日期:2016-12-16 00:00:00
abstract::The basic helix-loop-helix (bHLH) protein family has previously been shown to be involved in the development of mesodiencephalic dopaminergic (mdDA) neurons in the murine midbrain. Specifically, Ngn2 and Mash1 are known to have a role in the specification of neural progenitors in the ventricular zone (VZ) of the midbr...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2017.00353
更新日期:2017-11-01 00:00:00
abstract::The dorsal root ganglion (DRG) contains heterogeneous populations of sensory neurons including primary nociceptive neurons and C-fibers implicated in pain signaling. Recent studies have demonstrated DRG hyperexcitability associated with downregulation of A-type K(+) channels; however, the molecular correlate of the co...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/neuro.02.003.2009
更新日期:2009-07-07 00:00:00
abstract::MicroRNAs (miRNAs) are key post transcriptional regulators of their multiple target genes. However, the detailed profile of miRNA expression in Parkinson's disease, the second most common neurodegenerative disease worldwide and the first motor disorder has not been charted yet. Here, we report comprehensive miRNA prof...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2013.00010
更新日期:2013-05-13 00:00:00
abstract::Some therapeutic side-effects result from simultaneous activation of homolog receptors by the same ligand. Tropomyosin receptor kinases (TrkA, TrkB and TrkC) play a major role in the development and biology of neurons through neurotrophin signaling. The wide range of cross-interactions between Trk receptors and neurot...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2017.00130
更新日期:2017-05-03 00:00:00
abstract::Previous reports have shown that running wheel activity or voluntary exercise prevents hyperphagia and obesity in various animal models of obesity, but such effects seem only minimal in obese animals lacking leptin or leptin receptors. The mechanisms underlying this ineffectiveness remain unclear. Here, we identified ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2018.00179
更新日期:2018-05-29 00:00:00
abstract::Glycogen synthase kinase-3 (GSK-3) is central to multiple intracellular pathways including those activated by Wnt/β-catenin, Sonic Hedgehog, Notch, growth factor/RTK, and G protein-coupled receptor signals. All of these signals importantly contribute to neural development. Early attention on GSK-3 signaling in neural ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2011.00044
更新日期:2011-11-17 00:00:00
abstract::Alzheimer's disease (AD) is a progressive disease with early degeneration of the central cholinergic neurons. Currently, three of four AD drugs act by inhibiting the acetylcholine (ACh) degrading enzyme, acetylcholinesterase (AChE). Efficacy of these drugs depends on available amount of ACh, which is biosynthesized by...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2019.00239
更新日期:2019-10-11 00:00:00
abstract::Age-progressive neurodegenerative pathologies, including Alzheimer's disease (AD), are distinguished and diagnosed by disease-specific components of intra- or extra-cellular aggregates. Increasing evidence suggests that neuroinflammation promotes protein aggregation, and is involved in the etiology of neurological dis...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2019.00310
更新日期:2019-12-12 00:00:00
abstract::Microglia plays a critical role in neuroinflammation after ischemic stroke by releasing diverse inflammatory cytokines. Long non-coding RNA taurine up-regulated gene 1 (lncRNA TUG1) is widely expressed in adult brain and has been reported to participate in multiple biological processes associated with nervous system d...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2019.00215
更新日期:2019-09-10 00:00:00
abstract::The competitive ectodomain shedding of amyloid-β precursor protein (APP) by α-secretase and β-secretase, and the subsequent regulated intramembrane proteolysis by γ-secretase are the key processes in amyloid-β peptides (Aβ) generation. Previous studies indicate that secretases form binary complex and the interactions ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2018.00431
更新日期:2018-11-27 00:00:00
abstract::Rod and cone phosphodiesterase 6 (PDE6) are key effector enzymes of the vertebrate phototransduction pathway. Rod PDE6 consists of two catalytic subunits PDE6α and PDE6β and two identical inhibitory PDE6γ subunits, while cone PDE6 is composed of two identical PDE6α' catalytic subunits and two identical cone-specific P...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2018.00233
更新日期:2018-07-09 00:00:00