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ApoE oligodendrocyte

Xu Cui, Michael Chopp, Zhenggang Zhang, Rongwen Li, Alex Zacharek, Julie Landschoot-Ward, Poornima Venkat, Jieli Chen
BACKGROUND AND PURPOSE: ATP-binding cassette transporter A1 (ABCA1) is a major reverse cholesterol transporter and plays critical role in the formation of brain high-density lipoprotein (HDL) cholesterol. Apolipoprotein E (ApoE) is the most abundant apolipoprotein and transports cholesterol into cells in brain. ABCA1 and ApoE are upregulated by liver-X receptors. Activation of liver-X receptors has neurorestorative benefit for stroke. The current study investigates whether ABCA1/ApoE/HDL pathway mediates GW3965, a synthetic dual liver-X receptor agonist, induced neurorestoration after stroke...
February 2017: Stroke; a Journal of Cerebral Circulation
Mohammad Abdullah, Hiroshi Takase, Mari Nunome, Hiroyuki Enomoto, Jin-Ichi Ito, Jian-Sheng Gong, Makoto Michikawa
Exosomes are small extracellular vesicles secreted by variety of cell types such as neurons, astrocytes, and oligodendrocytes. It is suggested that exosomes play essential role in the maintenance of the neuronal functions and also in the clearance of amyloid-β (Aβ) from the brain. Aβ is well known to cause neuronal cell death, whereas little is known about its effect on astrocytes. In this study, we examined the effect of Aβ on release of exosomes from astrocytes in culture. We analyzed release of exosomes and apoE, both of which are known to remove/clear Aβ from the brain, in the culture medium of astrocytes...
July 2, 2016: Journal of Alzheimer's Disease: JAD
Stephanie L Adams, Kathy Tilton, James A Kozubek, Sudha Seshadri, Ivana Delalle
Genome-wide association studies have established BIN1 (Bridging Integrator 1) as the most significant late-onset Alzheimer disease (AD) susceptibility locus after APOE We analyzed BIN1 protein expression using automated immunohistochemistry on the hippocampal CA1 region in 19 patients with either no, mild, or moderate-to-marked AD pathology, who had been assessed by Clinical Dementia Rating and CERAD scores. We also examined the amygdala, prefrontal, temporal, and occipital regions in a subset of these patients...
August 2016: Journal of Neuropathology and Experimental Neurology
Dina Safina, Frederik Schlitt, Ramona Romeo, Thorsten Pflanzner, Claus U Pietrzik, Vasanthy Narayanaswami, Frank Edenhofer, Andreas Faissner
The LDL family of receptors and its member low-density lipoprotein receptor-related protein 1 (LRP1) have classically been associated with a modulation of lipoprotein metabolism. Current studies, however, indicate diverse functions for this receptor in various aspects of cellular activities, including cell proliferation, migration, differentiation, and survival. LRP1 is essential for normal neuronal function in the adult CNS, whereas the role of LRP1 in development remained unclear. Previously, we have observed an upregulation of LewisX (LeX) glycosylated LRP1 in the stem cells of the developing cortex and demonstrated its importance for oligodendrocyte differentiation...
August 2016: Glia
Valerio Leoni, Claudio Caccia
Huntington disease (HD), an autosomal dominant neurodegenerative disorder caused by an abnormal expansion of CAG trinucleotide repeat in the Huntingtin (HTT) gene, is characterized by extensive neurodegeneration of striatum and cortex and severe diffuse atrophy at MRI. The expression of genes involved in the cholesterol biosynthetic pathway and the amount of cholesterol, lanosterol, lathosterol and 24S-hydroxycholesterol were reduced in murine models of HD. In case of HD-patients, the decrease of plasma 24OHC follows disease progression proportionally to motor and neuropsychiatric dysfunction and MRI brain atrophy, together with lanosterol and lathosterol (markers of cholesterol synthesis), and 27-hydroxycholesterol...
August 2015: Biochimica et Biophysica Acta
Walter Maetzler, Anja Apel, Markus Langkamp, Christian Deuschle, Sarah Selina Dilger, Johannes Georg Stirnkorb, Claudia Schulte, Erwin Schleicher, Thomas Gasser, Daniela Berg
Naturally occurring autoantibodies (NAbs) against a number of potentially disease-associated cellular proteins, including Amyloid-beta1-42 (Abeta1-42), Alpha-synuclein (Asyn), myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), and S100 calcium binding protein B (S100B) have been suggested to be associated with neurodegenerative disorders, in particular Alzheimer's (AD) and Parkinson's disease (PD). Whereas the (reduced) occurrence of specific NAbs in AD is widely accepted, previous literature examining the relation of these NAb titres between PD patients and controls, as well as comparing these levels with demographic and clinical parameters in PD patients have produced inconsistent findings...
2014: PloS One
Valerio Leoni, Claudio Caccia
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by an abnormal expansion of a CAG repeat in the huntingtin gene. Neurodegeneration of striatum and cortex with a severe atrophy at MRI are common findings in HD. The expression of genes involved in the cholesterol biosynthetic pathway such as HMG-CoA reductase and the levels of cholesterol, lanosterol, lathosterol and 24S-hydroxycholesterol are reduced in the brain, striatum and cortex in several HD mouse models. Mutant huntingtin affects the maturation and translocation of SREBP and cannot up-regulate LXR...
April 11, 2014: Biochemical and Biophysical Research Communications
Agnieszka Ługowska, Małgorzata Musielak, Ewa Jamroz, Antoni Pyrkosz, Tomasz Kmieć, Anna Tylki-Szymańska, Małgorzata Bednarska-Makaruk
Metachromatic leukodystrophy (MLD) is a severe, neurodegenerative, metabolic disease which is caused by deficient activity of arylsulfatase A (ARSA). Sulfatides and other substrates of ARSA are stored in central and peripheral nervous systems, and in some other organs. Accumulated sulfatides are especially toxic to oligodendrocytes and Schwann cells leading to progressive demyelination. The kind of apolipoprotein E (apoE) isoform is of essential significance for the modulation of sulfatide quantity in the brain as apoE4 contains more sulfatides than apoE3...
September 10, 2013: Gene
Katherine Nelissen, Monique Mulder, Ilse Smets, Silke Timmermans, Karen Smeets, Marcel Ameloot, Jerome J A Hendriks
Cholesterol synthesis and transport in oligodendrocytes are essential for optimal myelination and remyelination in pathological conditions such as multiple sclerosis. However, little is known about cholesterol homeostasis in the myelin-forming oligodendrocytes. Liver X receptors (LXRs) are nuclear oxysterol receptors that regulate genes involved in cholesterol homeostasis and may therefore play an important role in de- and remyelination. We investigated whether LXRs regulate cholesterol homeostasis in oligodendrocytes...
January 2012: Journal of Neuroscience Research
Ana Navarro, Eva del Valle, Amalia Juárez, Eva Martinez, Cristina Ordóñez, Aurora Astudillo, Jorge Tolivia
Apolipoprotein D (apo D) is a lipocalin present in the nervous system that may be related to processes of reinnervation, regeneration and neuronal cell protection. On the other hand, apo D expression has been correlated, in some brain regions, with normal ageing and neurodegenerative diseases. To elucidate the regional and cellular expression of apo Din normal human brain during ageing, we performed a detailed and extensive study in samples of post-mortem human cerebral cortices. To achieve this study, slot-blot techniques, for protein and mRNA,as well as immunohistochemistry and hybridohistochemistry methods, were used...
March 2010: Age (2005-)
Harsimran S Saini, Rochelle P Coelho, Sravan K Goparaju, Puneet S Jolly, Michael Maceyka, Sarah Spiegel, Carmen Sato-Bigbee
We had found previously that neurotrophin-3 (NT-3) is a potent stimulator of cAMP-response element binding protein (CREB) phosphorylation in cultured oligodendrocyte progenitors. Here, we show that CREB phosphorylation in these cells is also highly stimulated by sphingosine-1-phosphate (S1P), a sphingolipid metabolite that is known to be a potent mediator of numerous biological processes. Moreover, CREB phosphorylation in response to NT-3 involves sphingosine kinase 1 (SphK1), the enzyme that synthesizes S1P...
December 2005: Journal of Neurochemistry
Ana Navarro, Eva Del Valle, Jorge Tolivia
Apolipoprotein D (Apo D) is a secreted lipocalin in the nervous system that may be related to processes of reinnervation and regeneration. Under normal conditions, Apo D is present in the central nervous system in oligodendrocytes, astrocytes, and some scattered neurons. To elucidate the regional and cellular distribution of Apo D in normal human brain, we performed double immunohistochemistry for glial fibrillary acidic protein (GFAP) and Apo D in samples of postmortem human cerebral and cerebellar cortices...
August 2004: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
A Nichols, I Martinou, K Maundrell, J C Martinou
The p75 neurotrophin receptor (p75NTR) is a death domain (DD) containing receptor of the TNF/FAS(APO-1) family. p75NTR has recently been shown to mediate apoptosis in certain types of neurons as well as in oligodendrocytes. The molecular mechanisms by which p75NTR stimulates apoptosis are still unknown. Here, we have tested whether overexpression of p75NTR could modulate survival of sympathetic neurons cultured in the presence or absence of NGF. Moreover, using the yeast two-hybrid system, we tested whether p75NTR intracellular domain was able to dimerize or interact with known DD-containing proteins including FADD, RIP, RAIDD and TRADD...
September 1998: Apoptosis: An International Journal on Programmed Cell Death
Y Nakamura, M Yamamoto, E Kumamaru
The very low density lipoprotein receptor (VLDLR) is a newly described receptor which binds to apolipoprotein E (apoE) specifically. The authors designed a synthetic peptide of 17 amino acids representing the N-terminus of the putative first ligand binding domain of human VLDLR, this being a unique domain for VLDLR. When the synthetic peptide was used as the antigen, two different monoclonal antibodies were obtained (anti-VLDLR1 and anti-VLDLR2). Expressional cloning revealed that anti-VLDLR1 recognized the variant form of VLDLR which lacks 84 bp of O-linked sugar domain and anti-VLDLR2 recognized the full length form of VLDLR...
December 20, 2001: Brain Research
S Casha, W R Yu, M G Fehlings
Apoptosis or programmed cell death has been reported after CNS trauma. However, the significance of this mechanism in the pathophysiology of spinal cord injury, in particular at the cervical level, requires further investigation. In the present study, we used the extradural clip compression model in the rat to examine the cellular distribution of apoptosis following cervical spinal cord injury, the relationship between glial apoptosis and post-traumatic axonal degeneration and the possible role of apo[apoptosis]-1, CD95 (FAS) and p75 in initiating post-traumatic glial apoptosis...
2001: Neuroscience
S Pouly, B Becher, M Blain, J P Antel
Interferon gamma (IFN-gamma) has been shown to be produced within multiple sclerosis (MS) lesions by infiltrating lymphocytes; systemic administration of this cytokine induces exacerbation of the disease. The aim of the current study was to establish the contribution of IFN-gamma to oligodendrocyte (OL) injury. Our studies utilized cultured human OLs, obtained by dissociation of surgically derived non-MS adult brain tissue. Neither cell survival nor myelin basic protein (MBP) gene expression were affected after 96 hours of treatment with IFN-gamma (100 U/ml), as assessed by LDH release, nucleosome enrichment assay, and RT-PCR...
April 2000: Journal of Neuropathology and Experimental Neurology
Q R Huang, S M Teutsch, M M Buhler, B H Bennetts, R N Heard, N Manolios, G J Stewart
The pathogenesis of multiple sclerosis is under strong genetic control involving several or more genes each of modest effect. Whilst the mechanisms underlying the pathogenesis of MS remain unknown, it has been hypothesised that either decreased apoptosis of autoreactive T cells in the CNS, or increased apoptosis of oligodendrocytes may play an important role. The Apo-1/Fas antigen (CD95), the gene for which is located in a chromosomal region showing linkage in MS genome screens, is a critical inducer of apoptosis and studies have shown aberrant expression of this molecule in MS, correlating with a decrease in T cell apoptosis or increase in CNS tissue damage...
February 2000: Multiple Sclerosis: Clinical and Laboratory Research
K Okuizumi
Alzheimer disease (AD) is by far the most common cause of dementia in humans. Massive accumulation of senile plaques and neurofibrillary tangles are characteristic neuropathological manifestations of the disease. Recent investigations have revealed the presence of apolipoprotein E (apoE) in these structures. Furthermore, APOE4, a specific allele of the apoE gene, is frequently associated with sporadic AD and late-onset familial AD. Now, APOE4 has been established as being a major risk factor for AD. Although apoE is one of numerous plasma lipoproteins, it is of particular interest because, unlike other lipoproteins that are mainly synthesized in the liver, apoE is also synthesized in astrocytes and oligodendrocytes in the central nervous system...
December 1999: Nihon Rinsho. Japanese Journal of Clinical Medicine
A Espinosa de los Monteros, S Kumar, P Zhao, C J Huang, R Nazarian, T Pan, S Scully, R Chang, J de Vellis
It has been established that oligodendrocytes, the myelin forming cells, participate in iron homeostasis through the synthesis and secretion of transferrin. Here we investigated whether a correlation exists between myelination, the commonly studied function of oligodendrocytes, and that of transferrin synthesis and secretion. We used a proteolipid protein mutant, the myelin deficient rat, whose condition is characterized by severe hypomyelination. We compared the ontogenic profile for transferrin gene expression in mutants with that of unaffected rat pups through northern blot analysis and in situ hybridization...
February 1999: Neurochemical Research
E Ghebremedhin, C Schultz, G Botez, U Rüb, I Sassin, E Braak, H Braak
Argyrophilic grain disease (AGD) is a distinct degenerative disorder of the human brain associated with the formation of abnormally phosphorylated tau protein. AGD-related cytoskeletal changes are known to affect specific subsets of nerve cells and oligodendrocytes. Here we demonstrate a remarkable association between the apolipoprotein E (ApoE) epsilon2 allele and AGD. Individuals afflicted with AGD (n = 48) reveal a significantly higher frequency of the epsilon2 allele compared with controls (n = 43) (22% versus 4%, P < 0...
September 1998: Acta Neuropathologica
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