Abstract:
:Structural rearrangements of chromosome 10 are frequently observed in glioblastoma multiforme and over 80 % of tumour samples archived in the catalogue of somatic mutations in cancer database had gene copy number loss for PI4K2A which encodes phosphatidylinositol 4-kinase type IIalpha. PI4K2A loss of heterozygosity mirrored that of PTEN, another enzyme that regulates phosphoinositide levels and also PIK3AP1, MINPP1, INPP5A and INPP5F. These results indicated a reduction in copy number for a set of phosphoinositide signalling genes that co-localise to chromosome 10q. This analysis was extended to a panel of phosphoinositide pathway genes on other chromosomes and revealed a number of previously unreported associations with glioblastoma multiforme. Of particular note were highly penetrant copy number losses for a group of X-linked phosphoinositide phosphatase genes OCRL, MTM1 and MTMR8; copy number amplifications for the chromosome 19 genes PIP5K1C, AKT2 and PIK3R2, and also for the phospholipase C genes PLCB1, PLCB4 and PLCG1 on chromosome 20. These mutations are likely to affect signalling and trafficking functions dependent on the PI(4,5)P2, PI(3,4,5)P3 and PI(3,5)P2 lipids as well as the inositol phosphates IP3, IP5 and IP6. Analysis of flanking genes with functionally unrelated products indicated that chromosomal instability as opposed to a phosphoinositide-specific process underlay this pattern of copy number variation. This in silico study suggests that in glioblastoma multiforme, karyotypic changes have the potential to cause multiple abnormalities in sets of genes involved in phosphoinositide metabolism and this may be important for understanding drug resistance and phosphoinositide pathway redundancy in the advanced disease state.
journal_name
Mol Neurobioljournal_title
Molecular neurobiologyauthors
Waugh MGdoi
10.1007/s12035-014-9034-9subject
Has Abstractpub_date
2016-01-01 00:00:00pages
621-630issue
1eissn
0893-7648issn
1559-1182pii
10.1007/s12035-014-9034-9journal_volume
53pub_type
杂志文章abstract::Pharmacoresistance in epilepsy is a major challenge to successful clinical therapy. Glucocorticoid receptor (GR) dysregulation can affect the underlying disease pathogenesis. We recently reported that local drug biotransformation at the blood-brain barrier is upregulated by GR, which controls drug-metabolizing enzymes...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-020-02043-9
更新日期:2020-11-01 00:00:00
abstract::Long-term potentiation (LTP), a long-lasting, activity-dependent increase in the strength of synaptic transmission, is one of the most intensively studied forms of synaptic plasticity in the mammalian brain. In the CA1 region of the hippocampus, the induction of LTP is likely to require a rise in postsynaptic calcium ...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/BF02935552
更新日期:1991-01-01 00:00:00
abstract::The ubiquitin-proteasome system (UPS) is the main intracellular pathway for modulated protein turnover, playing an important role in the maintenance of cellular homeostasis. It also exerts a protein quality control through degradation of oxidized, mutant, denatured, or misfolded proteins and is involved in many biolog...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/s12035-012-8391-5
更新日期:2013-04-01 00:00:00
abstract::Polyglutamine [poly(Q)] disorders are a class of trinucleotide repeat expansion neurodegenerative disorders which are dominantly inherited and progressively acquired with age. This group of disorders entail the characteristic formation of protein aggregates leading to widespread loss of neurons in different regions of...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-018-1160-3
更新日期:2019-02-01 00:00:00
abstract::We prepared and grafted tropomyosin receptor kinase B (TrkB) gene-transfected mesenchymal stem cells (TrkB-MSCs) into the ischemic penumbra and investigated whether electroacupuncture (EA) treatment could promote functional recovery from ischemic stroke. For the behavioral test, TrkB-MSCs+EA resulted in significantly ...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-018-1067-z
更新日期:2019-01-01 00:00:00
abstract::Following stroke, complete cellular death in the ischemic brain area may ensue, with remaining brain areas undergoing tissue remodelling to various degrees. Experience-dependent brain plasticity exerted through an enriched environment (EE) promotes remodelling after central nervous system injury, such as stroke. Post-...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-017-0461-2
更新日期:2018-03-01 00:00:00
abstract::Brain-derived neurotrophic factor (BDNF), in addition to its neurotrophic action, also possesses antioxidant activities. However, the underlying mechanisms remain to be fully defined. Sestrin2 is a stress-responsive gene implicated in the cellular defense against oxidative stress. Currently, the potential functions of...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-015-9357-1
更新日期:2016-08-01 00:00:00
abstract::The goal of this study was to evaluate if the immunohistochemical expression of alpha-3 neuronal nicotinic acetylcholine receptor subunit in sympathetic ganglia remains stable after brain death, determining the possible use of sympathetic thoracic ganglia from subjects after brain death as study group. The third left ...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-012-8235-3
更新日期:2012-04-01 00:00:00
abstract::Based on a multimodal drug design strategy for age-related neurodegenerative diseases, we have synthesized a multifunctional nontoxic, brain-permeable iron-chelating compound, M30, possessing the neuroprotective N-propargyl moiety of the anti-Parkinsonian drug, monoamine oxidase-B inhibitor, rasagiline and the antioxi...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-012-8304-7
更新日期:2012-08-01 00:00:00
abstract::Alzheimer's disease (AD) is the most common progressive neurodegenerative disorder. A defining hallmark of the AD brain is the presence of intraneuronal neurofibrillary tangles (NFTs) which are made up of abnormally modified tau, with aberrant phosphorylation being the most studied posttranslational modification (PTM)...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/s12035-020-02084-0
更新日期:2020-12-01 00:00:00
abstract::Sonic hedgehog (Shh) has been found to regulate the angiogenic growth factor such as VEGF, Ang-1, and Ang-2 during ischemic insults, but the underlying mechanism is not fully understood. In this study, we employed oxygen-glucose deprivation (OGD) in astrocytes to mimic the ischemia in vitro. We found that OGD could in...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-013-8395-9
更新日期:2013-06-01 00:00:00
abstract::Previous studies have shown that excessive alcohol drinking is associated with chronic pain development; however, the molecular mechanism underlying this association is poorly understood. In this study, we investigated the effect of chronic alcohol consumption on plantar incision-induced postsurgical pain. We observed...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-017-0639-7
更新日期:2018-05-01 00:00:00
abstract::Tonic inhibition mediated by ambient levels of GABA that activate extrasynaptic GABAA receptors emerges as an essential factor that tunes neuronal network excitability in vitro and shapes behavioral responses in vivo. To address the role of neuromodulatory transmitter systems on this type of inhibition, we employed pa...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-018-0984-1
更新日期:2018-11-01 00:00:00
abstract::The exocyst, an octameric protein complex consisting of Exoc1 through Exoc8, was first determined to regulate exocytosis by targeting vesicles to the plasma membrane in yeast to mice. In addition to this fundamental role, the exocyst complex has been implicated in other cellular processes. In this study, we investigat...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-017-0857-z
更新日期:2018-08-01 00:00:00
abstract::The striatum is divided into two compartments, the striosomes and extrastriosomal matrix, which differ in several cytochemical markers, input-output connections, and time of neurogenesis. Since it is thought that limbic, reward-related information and executive aspects of behavioral information may be differentially p...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/s12035-008-8023-2
更新日期:2008-04-01 00:00:00
abstract::Parkinson's disease and other synucleinopathies are characterized by the presence of intra-neuronal protein aggregates enriched in the presynaptic protein α-synuclein. α-synuclein is considered an intrinsically disordered 14 kDa monomer, and although poorly understood, its transition to higher-order multimeric species...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-016-0266-8
更新日期:2017-12-01 00:00:00
abstract::Antibodies are increasingly being used as tools to study the function of cell surface markers. Several types of responses may occur upon the selective binding of an antibody to an epitope on a receptor. Antibody binding may trigger signals that are normally transduced by endogenous ligands. Moreover, antibody binding ...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/BF02780606
更新日期:1993-04-01 00:00:00
abstract::Parkinson's disease (PD) is characterized by dopaminergic (DA) neuron death in the substantia nigra (SN) and subsequent striatal adaptations. Mice treated with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrimidine (MPTP) are widely used as a model for PD. To assess the validity of the MPTP mouse model for PD p...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-015-9103-8
更新日期:2016-04-01 00:00:00
abstract::Zika virus (ZIKV) infection is associated with abnormal functions of neuronal cells causing neurological disorders such as microcephaly in the newborns and Guillain-Barré syndrome in the adults. Typically, healthy brain growth is associated with normal neural stem cell proliferation, differentiation, and maturation. T...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/s12035-018-1263-x
更新日期:2019-04-01 00:00:00
abstract::Alzheimer's disease (AD) is a progressive neurodegenerative brain pathology and the most common form of dementia. Evidence suggests that extracellular vesicles (EVs) containing cytokines and microRNA are involved in inflammation regulation. The current study aimed to explore a potential impact of AD patients' EVs on d...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-020-02013-1
更新日期:2020-10-01 00:00:00
abstract::The endocannabinoid system (ECS) actively participates in several physiological processes within the central nervous system. Among such, its involvement in the downregulation of the N-methyl-D-aspartate receptor (NMDAr) through a modulatory input at the cannabinoid receptors (CBr) has been established. After its produ...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-018-1129-2
更新日期:2019-02-01 00:00:00
abstract::Hippocampus-dependent memories, such as social recognition (SRM), are modulated by neurogenesis. However, the precise role of newborn neurons in social memory processing is still unknown. We showed previously that 1 week of enriched environment (EE) is sufficient to increase neurogenesis in the hippocampus (HIP) and t...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-016-9922-2
更新日期:2017-07-01 00:00:00
abstract::Oxidative damage to the inner ear is responsible for several types of sensorineural deafness. Cochlear stria marginal cells (MCs) are thought to be vulnerable to such oxidative stress. Activated poly(ADP-ribose) polymerase 1 (PARP1) has been implicated in several diseases, but the effect of PARP1 on MCs subjected to o...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-015-9469-7
更新日期:2016-11-01 00:00:00
abstract::Five-prime repressor element under dual repression binding protein-1 (Freud-1)/CC2D1A is genetically linked to intellectual disability and implicated in neuronal development. Freud-1 represses the serotonin-1A (5-HT1A) receptor gene HTR1A by histone deacetylase (HDAC)-dependent or HDAC-independent mechanisms in 5-HT1A...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-016-0306-4
更新日期:2017-12-01 00:00:00
abstract::This study elucidated the potential antidepressant-like effect of prolonged Ropren® administration (8.6 mg/kg, orally, once daily for 28 days) using a β-amyloid (25-35) rat model of Alzheimer's disease following gonadectomy. The experimental model was created by intracerebroventricular injection of β-amyloid (25-35) i...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-016-9848-8
更新日期:2017-05-01 00:00:00
abstract::During development, neurons migrate to the cortex radially from periventricular germinative zones as well as tangentially from ganglionic eminences. The vast majority of cortical neurons settle radially in the cortical plate. Neuronal migration requires an exquisite regulation of leading edge extension, nuclear transl...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1385/MN:30:3:225
更新日期:2004-12-01 00:00:00
abstract::Stromal cell-derived factor-1 alpha (SDF-1a) or CXCL12 is an important cytokine with multiple functions in the brain during development and in adulthood. The inflammatory response initiated by spinal cord injury (SCI) involves the processing of interleukin-1beta (IL-1ß) and IL-18 mediated by caspase-1 which is under t...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-015-9203-5
更新日期:2016-07-01 00:00:00
abstract::Nicotinic acetylcholine receptors (AChRs) are a family of acetylcholine-gated cation channels that form the predominant excitatory neurotransmitter receptors on muscles and nerves in the peripheral nervous system. AChRs are also expressed on neurons in lower amounts throughout the central nervous system. AChRs are eve...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/BF02740634
更新日期:1997-10-01 00:00:00
abstract::Neurodegenerative diseases represent a heterogeneous group of disorders whose common characteristic is the progressive degeneration of neuronal structure and function. Although much knowledge has been accumulated on the pathophysiology of neurodegenerative diseases over the years, more efforts are needed to understand...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/s12035-018-1031-y
更新日期:2018-12-01 00:00:00
abstract::Neural stem cells (NSCs) are hitherto regarded as perspective candidates for cell transplantation in clinical therapies for multilevel spinal cord injury and function restoration. However, the extreme drawbacks of NSCs available for injury transplantation still represent a significant bottleneck in neural regeneration...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-016-0057-2
更新日期:2017-01-01 00:00:00