Publications by authors named "Nina Bauer"

16 Publications

  • Page 1 of 1

Cannabis use of patients with inflammatory bowel disease in Germany: a cross-sectional survey.

Z Gastroenterol 2021 Jun 22. Epub 2021 Jun 22.

Department for Internal and Integrative Medicine, Sozialstiftung Bamberg, Bamberg, Germany.

Background And Aims:  Progressive legalization and increasing utilization of medical cannabis open up potential new applications, including for inflammatory bowel disease (IBD). This study aimed to collect current figures on the use of and experience with cannabis among IBD patients in Germany.

Methods:  A 71-item questionnaire was mailed to a randomly selected representative sample of 1000 IBD patients.

Results:  Questionnaires were returned by 417 patients (mean age 49.1 ± 17.0 years; 55.8 % women; 43.4 % ulcerative colitis and 54.7 % Crohn's disease). Seventy-three respondents (17.5 %) stated past cannabis use for recreational purposes, while 12 users mentioned usage at the time the questionnaire was completed (2.9 %). Seventeen patients (4.1 %) indicated past use of cannabis, and 18 participants (4.3 %) reported current use of cannabis to treat IBD. Perceived benefits of cannabis use by its users included reduced abdominal pain, improved sleep quality, and relief of unease and worry. They reported lower quality of life and higher levels of anxiety or depression than non-users. Of notice, 52.9 % of cannabis users obtained their cannabis from the black market. A total of 76.5 % of former and 50 % of current users did not report their cannabis use to the physician.

Conclusion:  This survey reveals the largest data set on cannabis use among IBD patients in Germany, with the potential for further research. Cannabis is mainly procured from the black market, with unknown quality.
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http://dx.doi.org/10.1055/a-1400-2768DOI Listing
June 2021

Cryopreservation impairs 3-D migration and cytotoxicity of natural killer cells.

Nat Commun 2020 10 16;11(1):5224. Epub 2020 Oct 16.

Friedrich-Alexander University Erlangen-Nürnberg and University Hospital Erlangen, Department of Dermatology, Erlangen, Germany.

Natural killer (NK) cells are important effector cells in the immune response to cancer. Clinical trials on adoptively transferred NK cells in patients with solid tumors, however, have thus far been unsuccessful. As NK cells need to pass stringent safety evaluation tests before clinical use, the cells are cryopreserved to bridge the necessary evaluation time. Standard degranulation and chromium release cytotoxicity assays confirm the ability of cryopreserved NK cells to kill target cells. Here, we report that tumor cells embedded in a 3-dimensional collagen gel, however, are killed by cryopreserved NK cells at a 5.6-fold lower rate compared to fresh NK cells. This difference is mainly caused by a 6-fold decrease in the fraction of motile NK cells after cryopreservation. These findings may explain the persistent failure of NK cell therapy in patients with solid tumors and highlight the crucial role of a 3-D environment for testing NK cell function.
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http://dx.doi.org/10.1038/s41467-020-19094-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7568558PMC
October 2020

Downregulation of the microtubule associated protein tau impairs process outgrowth and myelin basic protein mRNA transport in oligodendrocytes.

Glia 2015 Sep 4;63(9):1621-35. Epub 2015 Apr 4.

Department for Neuroscience, Molecular Neurobiology, University of Oldenburg, Oldenburg, Germany.

Oligodendrocytes, the myelin forming cells of the CNS, are characterized by their numerous membranous extensions, which enwrap neuronal axons and form myelin sheaths. During differentiation oligodendrocytes pass different morphological stages, downregulate the expression of the proteoglycan NG2, and acquire major myelin specific proteins, such as myelin basic proteins (MBP) and proteolipid protein. MBP mRNA is transported in RNA granules along the microtubules (MTs) to the periphery and translated locally. MTs participate in the elaboration and stabilization of the myelin forming extensions and are essential for cellular sorting processes. Their dynamic properties are regulated by microtubule associated proteins (MAPs). The MAP tau is present in oligodendrocytes and involved in the regulation and stabilization of the MT network. To further elucidate the functional significance of tau in oligodendrocytes, we have downregulated tau by siRNA technology and studied the effects on cell differentiation and neuron-glia contact formation. The data show that tau knockdown impairs process outgrowth and leads to a decrease in MBP expression. Furthermore, MBP mRNA transport to distant cellular extensions is impaired and cells remain in the NG2 stage. In myelinating cocultures with dorsal root ganglion neurons, oligodendrocyte precursor cells after tau miR RNA lentiviral knockdown develop into NG2 positive cells with very long and thin processes, contacting axons loosely, but fail to form internodes. This demonstrates that tau is important for MBP mRNA transport and involved in process formation. The disturbance of the balance of tau leads to abnormalities in oligodendrocyte differentiation, neuron-glia contact formation and the early myelination process.
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http://dx.doi.org/10.1002/glia.22832DOI Listing
September 2015

Oligodendroglial p130Cas is a target of Fyn kinase involved in process formation, cell migration and survival.

PLoS One 2014 21;9(2):e89423. Epub 2014 Feb 21.

Institute of Physiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.

Oligodendrocytes are the myelinating glial cells of the central nervous system. In the course of brain development, oligodendrocyte precursor cells migrate, scan the environment and differentiate into mature oligodendrocytes with multiple cellular processes which recognize and ensheath neuronal axons. During differentiation, oligodendrocytes undergo dramatic morphological changes requiring cytoskeletal rearrangements which need to be tightly regulated. The non-receptor tyrosine kinase Fyn plays a central role in oligodendrocyte differentiation and myelination. In order to improve our understanding of the role of oligodendroglial Fyn kinase, we have identified Fyn targets in these cells. Purification and mass-spectrometric analysis of tyrosine-phosphorylated proteins in response to overexpressed active Fyn in the oligodendrocyte precursor cell line Oli-neu, yielded the adaptor molecule p130Cas. We analyzed the function of this Fyn target in oligodendroglial cells and observed that reduction of p130Cas levels by siRNA affects process outgrowth, the thickness of cellular processes and migration behavior of Oli-neu cells. Furthermore, long term p130Cas reduction results in decreased cell numbers as a result of increased apoptosis in cultured primary oligodendrocytes. Our data contribute to understanding the molecular events taking place during oligodendrocyte migration and morphological differentiation and have implications for myelin formation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0089423PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3931761PMC
January 2015

Moderate hypoxia followed by reoxygenation results in blood-brain barrier breakdown via oxidative stress-dependent tight-junction protein disruption.

PLoS One 2013 6;8(12):e82823. Epub 2013 Dec 6.

Institute of Physiology and Pathophysiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.

Re-canalization of cerebral vessels in ischemic stroke is pivotal to rescue dysfunctional brain areas that are exposed to moderate hypoxia within the penumbra from irreversible cell death. Goal of the present study was to evaluate the effect of moderate hypoxia followed by reoxygenation (MHR) on the evolution of reactive oxygen species (ROS) and blood-brain barrier (BBB) integrity in brain endothelial cells (BEC). BBB integrity was assessed in BEC in vitro and in microvessels of the guinea pig whole brain in situ preparation. Probes were exposed to MHR (2 hours 67-70 mmHg O2, 3 hours reoxygenation, BEC) or towards occlusion of the arteria cerebri media (MCAO) with or without subsequent reperfusion in the whole brain preparation. In vitro BBB integrity was evaluated using trans-endothelial electrical resistance (TEER) and transwell permeability assays. ROS in BEC were evaluated using 2',7'-dichlorodihydrofluorescein diacetate (DCF), MitoSox and immunostaining for nitrotyrosine. Tight-junction protein (TJ) integrity in BEC, stainings for nitrotyrosine and FITC-albumin extravasation in the guinea pig brain preparation were assessed by confocal microscopy. Diphenyleneiodonium (DPI) was used to investigate NADPH oxidase dependent ROS evolution and its effect on BBB parameters in BEC. MHR impaired TJ proteins zonula occludens 1 (ZO-1) and claudin 5 (Cl5), decreased TEER, and significantly increased cytosolic ROS in BEC. These events were blocked by the NADPH oxidase inhibitor DPI. MCAO with or without subsequent reoxygenation resulted in extravasation of FITC-albumin and ROS generation in the penumbra region of the guinea pig brain preparation and confirmed BBB damage. BEC integrity may be impaired through ROS in MHR on the level of TJ and the BBB is also functionally impaired in moderate hypoxic conditions followed by reperfusion in a complex guinea pig brain preparation. These findings suggest that the BBB is susceptible towards MHR and that ROS play a key role in this process.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0082823PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3855783PMC
July 2014

Making myelin basic protein -from mRNA transport to localized translation.

Front Cell Neurosci 2013 Sep 27;7:169. Epub 2013 Sep 27.

Institute of Physiology and Pathophysiology, University Medical Center of the Johannes Gutenberg University Mainz, Germany.

In the central nervous system (CNS) of most vertebrates, oligodendrocytes enwrap neuronal axons with extensions of their plasma membrane to form the myelin sheath. Several proteins are characteristically found in myelin of which myelin basic protein (MBP) is the second most abundant one after proteolipid protein. The lack of functional MBP in rodents results in a severe hypomyelinated phenotype in the CNS demonstrating its importance for myelin synthesis. Mbp mRNA is transported from the nucleus to the plasma membrane and is translated locally at the axon-glial contact site. Axonal properties such as diameter or electrical activity influence the degree of myelination. As oligodendrocytes can myelinate many axonal segments with varying properties, localized MBP translation represents an important part of a rapid and axon-tailored synthesis machinery. MBP's ability to compact cellular membranes may be problematic for the integrity of intracellular membranous organelles and can also explain why MBP is transported in oligodendrocytes in the form of an mRNA rather than as a protein. Here we review the recent findings regarding intracellular transport and signaling mechanisms leading to localized translation of Mbp mRNA in oligodendrocytes. More detailed insights into the MBP synthesis pathway are important for a better understanding of the myelination process and may foster the development of remyelination therapies for demyelinating diseases.
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http://dx.doi.org/10.3389/fncel.2013.00169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3784684PMC
September 2013

A thermoresponsive and chemically defined hydrogel for long-term culture of human embryonic stem cells.

Nat Commun 2013 ;4:1335

EaStChem, School of Chemistry, University of Edinburgh, Joseph Black Building, West Mains Road, Edinburgh EH9 3JJ, UK.

Cultures of human embryonic stem cell typically rely on protein matrices or feeder cells to support attachment and growth, while mechanical, enzymatic or chemical cell dissociation methods are used for cellular passaging. However, these methods are ill defined, thus introducing variability into the system, and may damage cells. They also exert selective pressures favouring cell aneuploidy and loss of differentiation potential. Here we report the identification of a family of chemically defined thermoresponsive synthetic hydrogels based on 2-(diethylamino)ethyl acrylate, which support long-term human embryonic stem cell growth and pluripotency over a period of 2-6 months. The hydrogels permitted gentle, reagent-free cell passaging by virtue of transient modulation of the ambient temperature from 37 to 15 °C for 30 min. These chemically defined alternatives to currently used, undefined biological substrates represent a flexible and scalable approach for improving the definition, efficacy and safety of human embryonic stem cell culture systems for research, industrial and clinical applications.
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http://dx.doi.org/10.1038/ncomms2341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3562446PMC
June 2013

Myelin basic protein synthesis is regulated by small non-coding RNA 715.

EMBO Rep 2012 Sep 29;13(9):827-34. Epub 2012 Jun 29.

Institute of Physiology and Pathophysiology, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, 55128 Mainz, Germany.

Oligodendroglial Myelin Basic Protein (MBP) synthesis is essential for myelin formation in the central nervous system. During oligodendrocyte differentiation, MBP mRNA is kept in a translationally silenced state while intracellularly transported, until neuron-derived signals initiate localized MBP translation. Here we identify the small non-coding RNA 715 (sncRNA715) as an inhibitor of MBP translation. SncRNA715 localizes to cytoplasmic granular structures and associates with MBP mRNA transport granule components. We also detect increased levels of sncRNA715 in demyelinated chronic human multiple sclerosis lesions, which contain MBP mRNA but lack MBP protein.
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http://dx.doi.org/10.1038/embor.2012.97DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3432817PMC
September 2012

Heterogeneous nuclear ribonucleoprotein (hnRNP) F is a novel component of oligodendroglial RNA transport granules contributing to regulation of myelin basic protein (MBP) synthesis.

J Biol Chem 2012 Jan 29;287(3):1742-54. Epub 2011 Nov 29.

Department of Biology, Molecular Cell Biology, Johannes Gutenberg University of Mainz, Bentzelweg 3, 55128 Mainz, Germany.

Myelin basic protein (MBP) is a major component of central nervous system (CNS) myelin. The absence of MBP results in the loss of almost all compact myelin in the CNS. MBP mRNA is sorted into RNA granules that are transported to the periphery of oligodendrocytes in a translationally inactive state. A central mediator of this transport process is the trans-acting factor heterogeneous nuclear ribonucleoprotein (hnRNP) A2 that binds to the cis-acting A2-response element in the 3'UTR of MBP mRNA. Recently, we found that activation of the Src family nonreceptor tyrosine kinase Fyn in oligodendrocytes leads to phosphorylation of hnRNP A2 and to increased translation of MBP mRNA. Here, we identify the RNA-binding protein hnRNP F as a novel component of MBP mRNA transport granules. It is associated with hnRNP A2 and MBP mRNA in cytoplasmic granular structures and is involved in post-transcriptional regulation of MBP expression. Fyn kinase activity results in phosphorylation of hnRNP F in the cytoplasm and its release from MBP mRNA and RNA granules. Our results define hnRNP F as a regulatory element of MBP expression in oligodendrocytes and imply an important function of hnRNP F in the control of myelin synthesis.
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http://dx.doi.org/10.1074/jbc.M111.235010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3265857PMC
January 2012

In vitro modeling of central nervous system myelination and remyelination.

Glia 2012 Jan 19;60(1):1-12. Epub 2011 Aug 19.

MRC Centre for Regenerative Medicine, Edinburgh MS Centre, Queen's Medical Research Centre, Little France Crescent, Edinburgh, UK.

This review aims to summarize the current techniques to study myelination and remyelination in culture systems. We attempt to put these into historical context, and to identify the strengths and weaknesses of each approach, which vary depending on the experimental question to be tested. We discuss the difficulty and importance of quantification of myelination and in particular remyelination. Finally, we provide our predictions of how these techniques will and should develop in the future.
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http://dx.doi.org/10.1002/glia.21231DOI Listing
January 2012

Membrane lipid modification by polyunsaturated fatty acids sensitizes oligodendroglial OLN-93 cells against oxidative stress and promotes up-regulation of heme oxygenase-1 (HSP32).

J Neurochem 2010 Apr 22;113(2):465-76. Epub 2010 Jan 22.

Institute of Brain Chemistry and Human Nutrition School of Medicine, London Metropolitan University, N7 8DB London, UK.

Polyunsaturated fatty acids (PUFA) are highly abundant in brain tissue, and docosahexaenoic acid (DHA) might protect cells from oxidative stress (OS) during inflammation and demyelinating disorders, but also might exert pro-oxidant effects. Here we investigated if PUFA supplements lead to heat shock protein induction, altered cell survival properties and stress responses to OS exerted by hydrogen peroxide in oligodendroglial OLN-93 cells. The data show that supplements of various fatty acids (FA) with 18-22 carbons chain length and 2-6 double bonds led to PUFA enrichment in cellular membranes. Depending on the degree of desaturation, FA-supplements caused the up-regulation of heme oxygenase-1 (HSP32), a stress protein inducible by OS, and an increase in sensitivity to hydrogen peroxide-treatment. DHA, with the highest number of double bonds, was most effective. Co-treatment with DHA and the lipophilic vitamin E analogue alpha-tocopherol, suppressed heme oxygenase-1 up-regulation and cell survival was restored. Analysis of the lipid profile demonstrates that alpha-tocopherol not only has antioxidant capacities, but also directly modified the PUFA profile in cell membranes. Enrichment with higher omega-3, -6 and -9 PUFA and an increase in the biosynthesis rate of very long chain fatty acids, mainly changed the FA profile of ethanolamine and serine phosphoglycerides.
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http://dx.doi.org/10.1111/j.1471-4159.2010.06611.xDOI Listing
April 2010

Physical forces in myelination and repair: a question of balance?

J Biol 2009 Sep 25;8(8):78. Epub 2009 Sep 25.

MRC Centre for Regenerative Medicine, Centre for Multiple Sclerosis Research, The University of Edinburgh, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.

A recent report in BMC Cell Biology examines how the balance of extracellular forces and intracellular contractions regulate the shape changes required for oligodendrocyte myelination. A failure of remyelination such as seen in multiple sclerosis could be caused by loss of this balance.
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http://dx.doi.org/10.1186/jbiol169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2776912PMC
September 2009

Role of the oligodendroglial cytoskeleton in differentiation and myelination.

Glia 2009 Dec;57(16):1691-705

MRC Centre for Regenerative Medicine, Centre for Multiple Sclerosis Research, The University of Edinburgh, Queen's Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom.

Oligodendrocytes, the myelin-forming cells of the central nervous system, are in culture characterized by an elaborate process network, terminating in flat membranous sheets that are rich in myelin-specific proteins and lipids, and spirally wrap axons forming a compact insulating layer in vivo. By analogy with other cell types, maintenance and stability of these processes, as well as the formation of the myelin sheath, likely rely on a pronounced cytoskeleton consisting of microtubules and microfilaments. While the specialized process of wrapping and compaction forming the myelin sheath is not well understood, considerably more is known about how cytoskeletal organization is mediated by extracellular and intracellular signals and other interaction partners during oligodendrocyte differentiation and myelination. Here, we review the current state of knowledge on the role of the oligodendrocyte cytoskeleton in differentiation with an emphasis on signal transduction mechanisms and will attempt to draw out implications for its significance in myelination.
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http://dx.doi.org/10.1002/glia.20885DOI Listing
December 2009

Down-regulation of wt1 expression in leukemia cell lines as part of apoptotic effect in arsenic treatment using two compounds.

Leuk Lymphoma 2006 Aug;47(8):1629-38

Department of Internal Medicine II, Hematology and Oncology, University Hospital, Johann Wolfgang Goethe University, Frankfurt, Germany.

Arsenic trioxide (As2O3) induces remission in patients with acute promyelocytic leukemia (APL). To better understand molecular mechanisms of arsenic actions, this study investigated the effect of two different arsenic compounds on gene expression of apoptosis and cellular proliferation related genes. The Wilms' tumor gene (wt1) is up-regulated in acute myeloid leukemia (AML) and a variety of leukemia cell lines. The expression of wt1 in these cells is proposed to have an anti-apoptotic effect. HL-60 and K562 were treated with arsenic trioxide (As2O3) and sodium arsenite (NaAsO2) at concentrations between 0 - 10 microM for up to 48 h. The induction of apoptosis was accompanied by down-regulation of hTERT and wt1 mRNA and protein expression but up-regulation of par-4. Low concentrations of 0.1 microM arsenic induced expression of the anti-apoptotic bcl-2 gene in both cell lines HL-60 and K562. There were no major differences encountered between compounds. After arsenic treatment of the leukemia cell lines HL-60 and K562 the up-regulation of par-4 may contribute to the induction of apoptosis rather than down-regulation of bcl-2. The therapeutic effect of arsenic is the induction of apoptosis by modulating the gene expression profile of pro- and anti-apoptotic genes including the wt1 gene.
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http://dx.doi.org/10.1080/10428190600625398DOI Listing
August 2006

The dynamic instability of microtubules is required for aggresome formation in oligodendroglial cells after proteolytic stress.

J Mol Neurosci 2006 ;29(2):153-68

University of Oldenburg, Department of Biology, Molecular Neurobiology, D-26111 Oldenburg, Germany.

University of Oldenburg, Department of Biology, Molecular Neurobiology, D-26111 Oldenburg, Germany Ubiquitinated tau-positive inclusion bodies in oligodendrocytes are consistent features in a variety of neurodegenerative disorders, and their formation points to an underlying incapacity of the protein quality control system that normally prevents the accumulation of misfolded proteins. To study the consequences of proteasomal impairment, we have used an oligodendroglial cell line, namely OLN-t40 cells, genetically engineered to express the longest human tau isoform. Treatment of OLN-t40 cells with the proteasomal inhibitor MG-132 (0.5 microM, 18 h) caused the formation of large, nonfibrillary tau-positive aggregates containing the small HSP alphaB-crystallin and ubiquitin in the vicinity of the microtubule organizing center (MTOC). The sequestration of misfolded proteins into specialized regions, called aggresomes, in response to stress stimuli has been reported to be associated with a redistribution of intermediate filaments (IFs). In oligodendroglial cells, which do not contain a cytoplasmic IF system, aggresomelike inclusions were instead surrounded by bundles of MTs and contained clusters of mitochondria. Aggresome formation was prevented by both MT-stabilizing and -destabilizing drugs, indicating not only that an intact cytoskeleton but also the dynamic instability of the MT network is required. Furthermore, the binding of stress-induced alphaBcrystallin to the MTs points to a possible protective role during disease progression.
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http://dx.doi.org/10.1385/JMN:29:2:153DOI Listing
April 2007

Tau-inclusion body formation in oligodendroglia: the role of stress proteins and proteasome inhibition.

Int J Dev Neurosci 2004 Nov;22(7):443-51

Department of Biology, University of Olderburg, PO Box 2503, D-26111 Oldenburg, Germany.

Filamentous tau-positive inclusions in neurons and glia are a unifying mechanism underlying a variety of late onset neurodegenerative disorders termed "tauopathies". Oligodendroglial lesions and white matter pathology have long been underestimated and are specifically prominent in frontotemporal dementias (FTDs), such as Pick's disease (PiD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17). Oligodendrocytes contain an extensive microtubule network and express the microtubule-associated protein tau. Tau-positive inclusion bodies in oligodendrocytes are positively stained with antibodies against ubiquitin and heat shock proteins (HSPs). Specifically the small HSP alphaB-crystallin has been identified in oligodendroglial lesions. HSPs act as molecular chaperones and prevent the accumulation of abnormal proteins, and support proteolytic degradation by targeting non-reparable proteins to the ubiquitin proteasomal pathway. HSPs and the proteasomal system closely work together. The present report summarizes recent data on HSP induction and aggregate formation in oligodendroglia cell culture systems, indicating that posttranslational modification of tau, HSP induction and alterations of the proteasomal system, which might occur during aging and disease processes, are involved in the neuropathological events leading to aggregate formation and degeneration.
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http://dx.doi.org/10.1016/j.ijdevneu.2004.07.003DOI Listing
November 2004
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