Disease relevance of NES

• Nestin is a potential mediator of malignancy in human neuroblastoma cells [1].
• Likewise, overexpression of the intermediate filament nestin, a neuroectodermal stem cell marker, is linked to increased aggressiveness in several nervous system tumors [1].
• In a series of 40 surgical specimens, including gliomas, vascular malformations, abscesses and angiomas, the glial reaction has been studied by immunohistochemistry and immunofluorescence of Nestin, GFAP and Vimentin [2].
• We show that the GL15 glioblastoma derived human cell line displays a high expression of nestin which, combined with the previously demonstrated high expression of vimentin, constitutes a characteristic of astrocyte restricted precursors [3].
• Reactive astrocytes in neurotrauma, stroke, or neurodegeneration are thought to undergo cellular hypertrophy, based on their morphological appearance revealed by immunohistochemical detection of glial fibrillary acidic protein, vimentin, or nestin, all of them forming intermediate filaments, a part of the cytoskeleton [4].
• These results specify a function for Nestin in cell motility and identify a novel pathway for prostate cancer metastasis [5].

Psychiatry related information on NES

• Beta-cell differentiation during human development does not rely on nestin-positive precursors: implications for stem cell-derived replacement therapy [6].
• Expression of nestin in Purkinje cells in patients with Creutzfeldt-Jakob disease [7].
• Nine NES tests evaluating psychomotor performance, visuospatial ability, memory, and mood were administered in approximately 40 minutes [8].
• The Neurobehavioral Evaluation System was designed for field studies of workers, but many NES tests can be performed satisfactorily by children as young as 7 or 8 years old and a few tests, such as simple reaction time, can be performed by preschool children [9].
• For this purpose, comparisons were made between scores on NES tests and traditional neuropsychological tests designed to measure functioning in the same cognitive domains in a sample of patients with idiopathic Parkinson's disease (PD) [10].

High impact information on NES

• Interestingly, an NES mutant of c-Fos, but not wild-type, substitutes ERK5 activity for HeLa cell proliferation [11].
• The number of immature glial cell fibers, expressing nestin, was not affected, but the proportion of mature glial cell fibers, expressing glial fibrillary acidic protein, was significantly decreased by both LID and MMI treatment of the dams [12].
• A nestin scaffold links Cdk5/p35 signaling to oxidant-induced cell death [13].
• The intermediate filament protein, nestin, has been implicated as an organizer of survival-determining signaling molecules [13].
• When nestin expression was related to the sensitivity of neural progenitor cells to oxidant-induced apoptosis, nestin displayed a distinct cytoprotective effect [13].

Chemical compound and disease context of NES

• Full-length atrophin-1 with 65 polyglutamine repeats and mutations inactivating the NES also yielded increased nuclear localization and increased toxicity [14].
• A construct with 65 glutamine repeats encoding an N-terminal fragment (which removes an NES) of atrophin-1 similar in size to the truncation product in DRPLA patient tissue, showed increased nuclear labeling, and an increase in cellular toxicity, compared with a similar fragment with 26 glutamines [14].
• Outside any period of acute exposure, the workers answered a self-administered questionnaire on neurotoxic symptoms, EUROQUEST, and performed six psychometric tests on a computer-assisted version of battery NES [15].
• Apart from that, a significant change was observed in 5/41 parameters being monitored (the pair t-test): I) decrease in the total NES score, II) decrease in the sensorial integration subscale NES score, III) increase in psychomotor speed, IV) decrease in auditory reaction time, V) increase in basal cortisol [16].
• The complex retroviruses encode a Rev protein that uses a leucine-rich NES to interact with CRM1 and the U snRNA-export pathway [17].

Biological context of NES

• Transfection studies that modulate N-Myc levels also result in commensurate changes in nestin mRNA and protein amounts as well as in cell proliferation and motility [1].
• Stable transfection of a nestin antisense sequence into neuroblastic, N-myc-amplified, LA1-55n cells results in a 2-fold reduction in nestin protein without altering N-Myc expression [1].
• Gel mobility shift assays show that N-Myc binds specifically to E-box sequences in the regulatory second intron of the nestin gene and nuclear run-off studies show that increases in N-Myc protein up-regulate nestin transcription rate [1].
• Interestingly, BMP-4, AFP, nestin and HNF-4alpha genes showed differential gene expression during ex vivo expansion [18].
• Oxidative stress in neuronal precursor cells led to downregulation of nestin with subsequent activation of cyclin-dependent kinase 5 (Cdk5), a crucial kinase in the nervous system [13].

Anatomical context of NES

• Subcellular fractionation and immunoblot studies indicate that nestin is present in the nucleus as well as in the cytoplasm of neuroblastoma cell lines [1].
• We observed that 5-bromodeoxyuridine (BrdU) + nestin double-labeled neural precursor cells increased in the spinal cords of Tg mice compared with non-Tg mice, with a much greater increase produced by EGF and FGF2 treatment [19].
• HLSCs were also positive for vimentin and nestin, a stem cell marker [20].
• In conclusion, nestin is expressed in the human kidney from the first steps of glomerulogenesis within podocytes, mesangial, and endothelial cells [21].
• Nestin was also detected in developing glomeruli within immature podocytes and a few other cells [21].

Associations of NES with chemical compounds

• METHODS: Formalin fixed, paraffin processed sections from two human foetuses, 16 brain tumours of both neuronal and glial lineage and two metastatic tumours were immunostained with polyclonal antibody to nestin [22].
• To further explore the neuroprotective mechanisms underlying HB1.F3 cell transplantation, we performed cell culture studies and found that a modest number of HB1.F3 cells were TH and dopamine and cAMP-regulated phosphoprotein 32 positive, although most cells were nestin positive, suggesting a mixed population of mature and immature cells [23].
• The induced cells were observed for morphological properties and detected for expressions of type II collagen, triglyceride or neuron-specific enolase and nestin [24].
• A 150-amino-acid fragment derived from the cloned nestin cDNA was coupled to glutathione S-transferase and used as an immunogen to generate a rabbit polyclonal antiserum that selectively detects human nestin [25].
• CONCLUSIONS: A subpopulation of human corneal stem cells exhibit neuronal properties in vitro, as evidenced by immunoreactivity to nestin, GABA receptor, glycine receptor, and serotonin receptor, as well as functional neurophysiological responses to GABA and kainic acid [26].

Physical interactions of NES

• Finally, DNA cross-linking experiments show that nestin binds DNA in N-myc-amplified N-type cell lines [1].
• Müller glial cells express nestin coupled with glial fibrillary acidic protein in experimentally induced glaucoma in the rat retina [27].

Co-localisations of NES

• The progenitor cell marker nestin also localizes asymmetrically in colcemid-treated hNPCs and colocalizes with LGN [28].

Regulatory relationships of NES

• Cells of glial lineage differentiated by down-regulating nestin expression and up-regulating GFAP expression [29].
• BMSC cultured in the presence of EGF or BDNF expressed the protein and mRNA for nestin, a marker of neural precursors [30].
• Approximately, 60 +/- 8% of CD133 expressing cells expressed nestin [31].
• In this in vitro assay system, nestin is up-regulated after local application of Bone Morphogenetic Protein 2 and 4 [32].
• Indeed, NXT1 stimulates nuclear protein export of the NES-containing protein PKI in vitro [33].

Other interactions of NES

• Thus, nestin may be one mediator of N-myc-associated tumor aggressiveness of human neuroblastoma [1].
• Thus, 7 days after neural induction the majority of cells were NE, expressing nestin, Sox1, and Pax6 [34].
• Confocal microscopy demonstrated that adult glomeruli display nestin immunoreactivity in vimentin-expressing cells with the podocyte morphology and not in cells bearing the endothelial marker CD31 [21].
• Western blotting of the intermediate filament-enriched cytoskeletal fraction and coimmunoprecipitation of nestin with anti-CDK5 antibodies confirmed these results [21].
• In the invading tumor, developing positive astrocytes were hardly distinguishable from tumor invading astrocytes that, interestingly, were much more Nestin- than GFAP-positive [2].

Analytical, diagnostic and therapeutic context of NES

• Confocal microscopy of experiments conducted with antibodies against nestin and endothelial markers demonstrated that endothelial cells belonging to capillaries invading the lower cleft of S-shaped bodies and the immature glomeruli were nestin immunoreactive [21].
• Transplantation of nestin+ cells and fetal pancreatic fibroblasts into athymic mice also failed to result in the development of beta-cells, whereas nestin- fetal pancreatic epithelial cells gave rise to functional insulin-secreting beta-cells [35].
• Nestin expression increased after treatment, whereas GFAP immunostaining was not significantly modified [36].
• In all cell cultures, nestin costained with the neuroepithelial cell marker vimentin [25].
• Cloning and sequence analysis of the rat and human nestin second introns revealed local domains of high sequence similarity in the 3' portion of the introns [37].

References