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 (e.g., cytochrome P450s, CYPs) and efflux drug transporters (MDR1) in human epileptic brain endothelial cells (EPI-ECs). Here, we establish that this mechanism is influenced upstream by GR and its association with heat shock proteins/co-chaperones (Hsps) during maturation, which differentially affect human epileptic (EPI) tissue and brain endothelial cells. Overexpressed GR, Hsp90, Hsp70, and Hsp40 were found in EPI vs. NON-EPI brain regions. Elevated neurovascular GR expression and co-localization with Hsps was evident in the EPI regions with cortical dysplasia, predominantly in the brain micro-capillaries and neurons. A corresponding increase in ATPase activity (*p < 0.05) was found in the EPI regions. The GR-Hsp90/Hsp70 binding patterns indicated a faster chaperone-promoted maturation of GR, leading to its overactivation in both the tissue and EPI-ECs derived from EPI/focal regions and GR silencing in EPI-ECs slowed such GR-Hsp interactions. Significantly accelerated GR nuclear translocation was determined in EPI-ECs following treatment with GR modulators/ligands dexamethasone, rifampicin, or phenytoin. Our findings reveal that overexpressed GR co-localizes with Hsps in the neurovasculature of EPI brain, increased GR maturation by Hsps accelerates EPI GR machinery, and furthermore this change in EPI and NON-EPI GR-Hsp interaction alters with the age of seizure onset in epileptic patients, together affecting the pathophysiology and drug regulation in the epileptic brain endothelium.
journal_name
Mol Neurobioljournal_title
Molecular neurobiologyauthors
Hossain M,Williams S,Ferguson L,Bingaman W,Ghosh A,Najm IM,Ghosh Cdoi
10.1007/s12035-020-02043-9subject
Has Abstractpub_date
2020-11-01 00:00:00pages
4511-4529issue
11eissn
0893-7648issn
1559-1182pii
10.1007/s12035-020-02043-9journal_volume
57pub_type
杂志文章abstract::Cyclin-dependent kinases (Cdks) play a key role in orchestrating the coordination of cell cycle progression in proliferating cells. The escape from the proper control of the cell cycle by the upregulation of cyclins or aberrant activation of Cdks leads to malignant transformation. In quiescent cells and/or terminally ...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1385/mn:34:1:27
更新日期:2006-08-01 00:00:00
abstract::Heterogenous nuclear ribonucleoproteins (hnRNPs) are a complex and functionally diverse family of RNA binding proteins with multifarious roles. They are involved, directly or indirectly, in alternative splicing, transcriptional and translational regulation, stress granule formation, cell cycle regulation, and axonal t...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/s12035-020-02137-4
更新日期:2021-02-01 00:00:00
abstract::Activation of RhoA/Rho kinase leads to growth cone collapse and neurite retraction. Although RhoA/Rho kinase inhibition has been shown to improve axon regeneration, remyelination and functional recovery, its role in neuronal cell death remains unclear. To determine whether RhoA/Rho kinase played a role in neuronal dea...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-016-0187-6
更新日期:2017-11-01 00:00:00
abstract::Voltage-dependent Ca2+ channels are important in the regulation of neuronal structure and function, and as a result, they have received considerable attention. Recent studies have begun to characterize the diversity of their properties and the relationship of this diversity to their various cellular functions. In part...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/BF02740620
更新日期:1997-02-01 00:00:00
abstract::The complex multifactorial nature of AD pathogenesis has been highlighted by evidence implicating additional neurodegenerative mechanisms, beyond that of amyloid-β (Aβ) and tau. To provide insight into cause and effect, we here investigated the temporal profile and associations of pathological changes in synaptic, end...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-020-01950-1
更新日期:2020-08-01 00:00:00
abstract::The neural crest is a transient embryonic structure that gives rise to a multitude of different cell types in the vertebrate. As such, it is an ideal model to study the processes of vertebrate differentiation and development. This review focuses on two major questions related to neural crest development. The first que...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/BF02935639
更新日期:1993-07-01 00:00:00
abstract::CX3CL1 (fractalkine) is the only member of the CX3C (delta) subfamily of chemokines which is unique and combines the properties of both chemoattractant and adhesion molecules. The two-form ligand can exist either in a soluble form, like all other chemokines, and as a membrane-anchored molecule. CX3CL1 discloses its bi...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/s12035-016-9787-4
更新日期:2017-04-01 00:00:00
abstract::The characteristic functions of tissues and organs result from the integrated activity of individual cells. Nowhere is this more evident than in the nervous system, where the activities of single neurons communicating via electrical and chemical signals mediate complex functions, such as learning and memory. The past ...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/BF02740623
更新日期:1996-12-01 00:00:00
abstract::Parkinson's disease and dementia with Lewy bodies are major challenges in research and clinical medicine world-wide and contribute to the most common neurodegenerative disorders. Previously, specific mitochondrial polymorphisms have been found to enhance clearance of amyloid-β from the brain of APP-transgenic mice lea...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-015-9399-4
更新日期:2016-09-01 00:00:00
abstract::Once infected by HIV-1, microglia abundantly produce accessory protein Nef that enhances virus production and infectivity, but little is known about its intracellular compartmentalization, trafficking mode(s), and release from microglia. Here, we transfected immortalized human microglia with a plasmid encoding Nef tag...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-018-1072-2
更新日期:2019-01-01 00:00:00
abstract::Information processing in neurobiological systems is commonly thought to rely on the assessment of a signal-to-noise ratio as the key mechanism of signal detection; it assumes and requires that both signal and noise are concurrently available. An alternative theory holds that detection proceeds by the system appreciat...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1385/MN:24:1-3:145
更新日期:2001-08-01 00:00:00
abstract::Iron accumulates progressively in the brain with age, and iron-induced oxidative stress has been considered as one of the initial causes for Alzheimer's disease (AD) and Parkinson's disease (PD). Based on the role of hepcidin in peripheral organs and its expression in the brain, we hypothesized that this peptide has a...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-014-8847-x
更新日期:2015-08-01 00:00:00
abstract::Neurons are able to adjust the sensitivity of receptor-mediated processes according to the level of receptor activation. Extrapolating from our knowledge of other cellular proteins, regulation of receptor mRNA availability would provide a highly economical means of achieving this objective. Epidermal growth factor is ...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/BF02769175
更新日期:1993-10-01 00:00:00
abstract::Agmatine, an endogenous neuromodulator, is a potential candidate to constitute an adjuvant/monotherapy for the management of depression. A recent study by our group demonstrated that agmatine induces Nrf2 and protects against corticosterone effects in a hippocampal neuronal cell line. The present study is an extension...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-015-9182-6
更新日期:2016-07-01 00:00:00
abstract::Neonatal hypoxic-ischemic (HI) injury still remains an important issue as it is a major cause of neonatal death and neurological dysfunctions. Currently, there are no well-established treatments to reduce brain damage and its long-term sequel in infants. Recently, reported data show that histone deacetylase inhibitors...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-016-0049-2
更新日期:2017-09-01 00:00:00
abstract::Tonic GABAA receptors are a subpopulation of receptors that generate long-lasting inhibition and thereby control network excitability. In recent years, these receptors have been implicated in various neurological and psychiatric disorders, including Parkinson's disease, schizophrenia, and epilepsy. Their distinct subu...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/s12035-015-9423-8
更新日期:2016-10-01 00:00:00
abstract::Morphine as an opioid is an important drug in the treatment of moderate to severe pain. Several stress factors via generation of nitric oxide (NO) and oxidative stress (OS) are responsible for the adverse effects of morphine-induced analgesia, addiction, and antinociceptive tolerance, including altered Ca2+ concentrat...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-020-01975-6
更新日期:2020-08-01 00:00:00
abstract::Many studies have shown that mitochondrial dysfunction and the subsequent oxidative stress caused by excessive reactive oxygen species (ROS) generation play a central role in the pathogenesis of Parkinson's disease (PD). We have previously shown that low-intensity ultrasound (LIUS) could reduce ROS generation by L-but...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-016-0104-z
更新日期:2017-10-01 00:00:00
abstract::Prion pathologies are characterized by the conformational conversion of the cellular prion protein (PrPC) into a pathological infectious isoform, known as PrPSc. The latter acquires different abnormal conformations, which are associated with specific pathological phenotypes. Recent evidence suggests that prions adapt ...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-018-1279-2
更新日期:2019-04-01 00:00:00
abstract::There is robust evidence that major depression (MDD) is accompanied by a low-grade activation of the immune-inflammatory response system, which is involved in the pathophysiology of this disorder. It is also becoming apparent that glia cells are in reciprocal communication with neurons, orchestrate various neuromodula...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/s12035-020-01961-y
更新日期:2020-10-01 00:00:00
abstract::The Peruvian plant Lepidium meyenii (Maca) has been shown to possess neuroprotective activity both in vitro and in vivo. Previous studies have also demonstrated the activity of the pentane extract and its macamides, the most representative lipophilic constituents of Maca, in the endocannabinoid system as fatty acid am...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-013-8499-2
更新日期:2013-10-01 00:00:00
abstract::Neurons are highly polarized cells displaying an elaborate architectural morphology. The design of their dendritic arborization and the distribution of their synapses contribute importantly to information processing in the brain. The growth and complexity of dendritic arbors are driven by the formation of synapses alo...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-018-1378-0
更新日期:2019-07-01 00:00:00
abstract::Resveratrol is a natural compound that mimics the antioxidant and antiaging effects of caloric restriction, mainly mediated through SIRT1, a deacetylase that induces longevity and neuroprotection. We aimed to analyze the effects of resveratrol on the brain status of control non-transgenic (NoTg) and AD transgenic (3xT...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-018-1157-y
更新日期:2019-02-01 00:00:00
abstract::Ischemic stroke, caused by obstruction of blood flow to the brain, would initiate microglia activation which contributes to neuronal damage. Therefore, inhibition of microglia-mediated neuroinflammation could be a therapeutic strategy for ischemic stroke. This study was aimed to elucidate the anti-inflammatory effects...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-015-9418-5
更新日期:2016-09-01 00:00:00
abstract::There is considerable attention being given to the association of Alzheimer's disease and cholesterol homeostasis. To that end, some have suggested that elevated cholesterol levels are a risk factor for Alzheimer's disease. If elevated cholesterol is a risk factor for Alzheimer's disease, then it would be expected tha...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1385/MN:31:1-3:185
更新日期:2005-01-01 00:00:00
abstract::Microglia, the resident macrophages of the central nervous system, rapidly activate in nearly all kinds of neurological diseases. These activated microglia become highly motile, secreting inflammatory cytokines, migrating to the lesion area, and phagocytosing cell debris or damaged neurons. During the past decades, th...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/s12035-013-8620-6
更新日期:2014-06-01 00:00:00
abstract::Amyloid-β oligomers (AβOs) toxicity causes mitochondrial dysfunction, leading to synaptic failure in Alzheimer's disease (AD). Considering presynaptic high energy demand and tight Ca2+ regulation, impairment of mitochondrial function can lead to deteriorated neural activity and cell death. In this study, an AD mouse m...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-020-02064-4
更新日期:2020-11-01 00:00:00
abstract::Emerging researches point to a relevant role of postsynaptic density (PSD) proteins, such as PSD-95, Homer, Shank, and DISC-1, in the pathophysiology of schizophrenia and autism spectrum disorders. The PSD is a thickness, detectable at electronic microscopy, localized at the postsynaptic membrane of glutamatergic syna...
journal_title:Molecular neurobiology
pub_type: 杂志文章,评审
doi:10.1007/s12035-013-8534-3
更新日期:2014-02-01 00:00:00
abstract::A great deal of attention has been paid to neuroprotective therapies for cerebral ischemic stroke. Our two recent clinical trials showed that ginsenoside Rd (Rd), a kind of monomeric compound extracted from Chinese herbs, Panax ginseng and Panax notoginseng, was safe and efficacious for the treatment of ischemic strok...
journal_title:Molecular neurobiology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s12035-015-9261-8
更新日期:2016-05-01 00:00:00
abstract::Although the use, and misuse, of methylphenidate is increasing in childhood and adolescence, there is little information about the consequences of this psychostimulant chronic use on brain and behavior during development. The aim of the present study was to investigate hippocampus biochemical, histochemical, and behav...
journal_title:Molecular neurobiology
pub_type: 杂志文章
doi:10.1007/s12035-016-9987-y
更新日期:2017-08-01 00:00:00