Nerve Tissue Proteins

Publication Title: 
The Journal of Infectious Diseases

Plasma levels of interleukin (IL)-6, soluble IL-6 receptor, soluble gp130, leukemia inhibitory factor (LIF), and ciliary neutrophic factor (CNTF) were analyzed in 32 patients with severe malaria. Ten had renal failure, 8 had cerebral malaria, and 14 had other causes of severity. Before treatment, the IL-6 and soluble IL-6 receptor plasma levels were significantly higher in persons with cerebral malaria or renal failure than in other groups (P<.01 for both). After initiation of therapy, IL-6 levels dropped within 24 h, but soluble IL-6 receptor levels increased.

Author(s): 
Wenisch, C.
Linnau, K. F.
Looaresuwan, S.
Rumpold, H.
Publication Title: 
The Journal of Neuroscience: The Official Journal of the Society for Neuroscience

There is substantial evidence that bioenergetic defects and excitotoxicity may play a role in the pathogenesis of Huntington's disease (HD). Potential therapeutic strategies for neurodegenerative diseases in which there is reduced energy metabolism and NMDA-mediated excitotoxicity are the administration of the mitochondrial cofactor coenzyme Q10 and the NMDA antagonist remacemide.

Author(s): 
Ferrante, Robert J.
Andreassen, Ole A.
Dedeoglu, Alpaslan
Ferrante, Kimberly L.
Jenkins, Bruce G.
Hersch, Steven M.
Beal, M. Flint
Publication Title: 
Science (New York, N.Y.)

Huntington's disease (HD) is an inherited neurodegenerative disease caused by expansion of a polyglutamine tract in the huntingtin protein. Transcriptional dysregulation has been implicated in HD pathogenesis. Here, we report that huntingtin interacts with the transcriptional activator Sp1 and coactivator TAFII130. Coexpression of Sp1 and TAFII130 in cultured striatal cells from wild-type and HD transgenic mice reverses the transcriptional inhibition of the dopamine D2 receptor gene caused by mutant huntingtin, as well as protects neurons from huntingtin-induced cellular toxicity.

Author(s): 
Dunah, Anthone W.
Jeong, Hyunkyung
Griffin, April
Kim, Yong-Man
Standaert, David G.
Hersch, Steven M.
Mouradian, M. Maral
Young, Anne B.
Tanese, Naoko
Krainc, Dimitri
Publication Title: 
The Journal of Neuroscience: The Official Journal of the Society for Neuroscience

Huntington's disease (HD) results from polyglutamine expansion in huntingtin (htt), a protein with several consensus caspase cleavage sites. Despite the identification of htt fragments in the brain, it has not been shown conclusively that htt is cleaved by caspases in vivo. Furthermore, no study has addressed when htt cleavage occurs with respect to the onset of neurodegeneration. Using antibodies that detect only caspase-cleaved htt, we demonstrate that htt is cleaved in vivo specifically at the caspase consensus site at amino acid 552.

Author(s): 
Wellington, Cheryl L.
Ellerby, Lisa M.
Gutekunst, Claire-Anne
Rogers, Danny
Warby, Simon
Graham, Rona K.
Loubser, Odell
van Raamsdonk, Jeremy
Singaraja, Roshni
Yang, Yu-Zhou
Gafni, Juliette
Bredesen, Dale
Hersch, Steven M.
Leavitt, Blair R.
Roy, Sophie
Nicholson, Donald W.
Hayden, Michael R.
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

Huntington's disease (HD) is a neurodegenerative disease caused by polyglutamine (polyQ) expansion in the protein huntingtin (htt). Pathogenesis in HD seems to involve the formation of neuronal intranuclear inclusions and the abnormal regulation of transcription and signal transduction. To identify previously uncharacterized htt-interacting proteins in a simple model system, we used a yeast two-hybrid screen with a Caenorhabditis elegans activation domain library. We found a predicted SH3 domain protein (K08E3.3b) that interacts with N-terminal htt in two-hybrid tests.

Author(s): 
Holbert, Sébastien
Dedeoglu, Alpaslan
Humbert, Sandrine
Saudou, Frédéric
Ferrante, Robert J.
Neri, Christian
Publication Title: 
American Journal of Physiology. Endocrinology and Metabolism

Articular cartilage is an avascular, non-insulin-sensitive tissue that utilizes glucose as the main energy source, a precursor for glycosaminoglycan synthesis, and a regulator of gene expression. Facilitated glucose transport represents the first rate-limiting step in glucose metabolism. Previously, we demonstrated that glucose transport in chondrocytes is regulated by proinflammatory cytokines via upregulation of GLUT mRNA and protein expression.

Author(s): 
Shikhman, Alexander R.
Brinson, Diana C.
Lotz, Martin K.
Publication Title: 
The Journal of Biological Chemistry

Cell culture work suggests that signaling to polymerize cortical filamentous actin (F-actin) represents a required pathway for the optimal redistribution of the insulin-responsive glucose transporter, GLUT4, to the plasma membrane. Recent in vitro study further suggests that the actin-regulatory neural Wiskott-Aldrich syndrome protein (N-WASP) mediates the effect of insulin on the actin filament network. Here we tested whether similar cytoskeletal mechanics are essential for insulin-regulated glucose transport in isolated rat epitrochlearis skeletal muscle.

Author(s): 
Brozinick, Joseph T.
Hawkins, Eric D.
Strawbridge, Andrew B.
Elmendorf, Jeffrey S.
Publication Title: 
The Journal of Neuroscience: The Official Journal of the Society for Neuroscience

Huntington's disease (HD) is a fully penetrant autosomal-dominant inherited neurological disorder caused by expanded CAG repeats in the Huntingtin gene. Transcriptional dysfunction, excitotoxicity, and oxidative stress have all been proposed to play important roles in the pathogenesis of HD. This study was designed to explore the therapeutic potential of mithramycin, a clinically approved guanosine-cytosine-rich DNA binding antitumor antibiotic.

Author(s): 
Ferrante, Robert J.
Ryu, Hoon
Kubilus, James K.
D'Mello, Santosh
Sugars, Katharine L.
Lee, Junghee
Lu, Peiyuan
Smith, Karen
Browne, Susan
Beal, M. Flint
Kristal, Bruce S.
Stavrovskaya, Irina G.
Hewett, Sandra
Rubinsztein, David C.
Langley, Brett
Ratan, Rajiv R.
Publication Title: 
Stem Cells (Dayton, Ohio)

Mesenchymal stem cells (MSCs) exhibit immune-suppressive properties, follow a pattern of multilineage differentiation, and exhibit transdifferentiation potential. Ease in expansion from adult bone marrow, as well as its separation from ethical issues, makes MSCs appealing for clinical application. MSCs treated with retinoic acid resulted in synaptic transmission, based on immunostaining of synaptophysin and electrophysiological studies. In situ hybridization indicated that the neurotransmitter gene preprotachykinin-I was expressed in these cells.

Author(s): 
Cho, Kyung Jin
Trzaska, Katarzyna A.
Greco, Steven J.
McArdle, Joseph
Wang, Fu Shun
Ye, Jiang-Hong
Rameshwar, Pranela
Publication Title: 
The Journal of Pharmacology and Experimental Therapeutics

Glucans are immunomodulatory carbohydrates found in the cell walls of fungi and certain bacteria. We examined the pharmacokinetics of three water-soluble glucans (glucan phosphate, laminarin, and scleroglucan) after oral administration of 1 mg/kg doses in rats. Maximum plasma concentrations for glucan phosphate occurred at 4 h. In contrast, laminarin and scleroglucan showed two plasma peaks between 0.5 and 12 h. At 24 h, 27 +/- 3% of the glucan phosphate and 20 +/- 7% of the laminarin remained in the serum. Scleroglucan was rapidly absorbed and eliminated.

Author(s): 
Rice, Peter J.
Adams, Elizabeth L.
Ozment-Skelton, Tammy
Gonzalez, Andres J.
Goldman, Matthew P.
Lockhart, Brent E.
Barker, Luke A.
Breuel, Kevin F.
Deponti, Warren K.
Kalbfleisch, John H.
Ensley, Harry E.
Brown, Gordon D.
Gordon, Siamon
Williams, David L.

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