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Full-Text Articles in Medicine and Health Sciences

Triterpenoid Modulation Of Il-17 And Nrf-2 Expression Ameliorates Neuroinflammation And Promotes Remyelination In Autoimmune Encephalomyelitis, Tej K. Pareek, Abdelmadjid Belkadi, Sashi Kesavapany, Anita Zaremba, Sook L. Loh, Lianhua Bai, Mark L. Cohen, Colin Meyer, Karen T. Liby, Robert H. Miller, Michael B. Sporn, John J. Letterio Dec 2011

Triterpenoid Modulation Of Il-17 And Nrf-2 Expression Ameliorates Neuroinflammation And Promotes Remyelination In Autoimmune Encephalomyelitis, Tej K. Pareek, Abdelmadjid Belkadi, Sashi Kesavapany, Anita Zaremba, Sook L. Loh, Lianhua Bai, Mark L. Cohen, Colin Meyer, Karen T. Liby, Robert H. Miller, Michael B. Sporn, John J. Letterio

Dartmouth Scholarship

Inflammatory cytokines and endogenous anti-oxidants are variables affecting disease progression in multiple sclerosis (MS). Here we demonstrate the dual capacity of triterpenoids to simultaneously repress production of IL-17 and other pro-inflammatory mediators while exerting neuroprotective effects directly through Nrf2-dependent induction of anti-oxidant genes. Derivatives of the natural triterpene oleanolic acid, namely CDDO-trifluoroethyl-amide (CDDO-TFEA), completely suppressed disease in a murine model of MS, experimental autoimmune encephalomyelitis (EAE), by inhibiting Th1 and Th17 mRNA and cytokine production. Encephalitogenic T cells recovered from treated mice were hypo-responsive to myelin antigen and failed to adoptively transfer the disease. Microarray analyses showed significant suppression of …


Fus Transgenic Rats Develop The Phenotypes Of Amyotrophic Lateral Sclerosis And Frontotemporal Lobar Degeneration., Cao Huang, Hongxia Zhou, Jianbin Tong, Han Chen, Yong-Jian Liu, Dian Wang, Xiaotao Wei, Xu-Gang Xia Mar 2011

Fus Transgenic Rats Develop The Phenotypes Of Amyotrophic Lateral Sclerosis And Frontotemporal Lobar Degeneration., Cao Huang, Hongxia Zhou, Jianbin Tong, Han Chen, Yong-Jian Liu, Dian Wang, Xiaotao Wei, Xu-Gang Xia

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Fused in Sarcoma (FUS) proteinopathy is a feature of frontotemporal lobar dementia (FTLD), and mutation of the fus gene segregates with FTLD and amyotrophic lateral sclerosis (ALS). To study the consequences of mutation in the fus gene, we created transgenic rats expressing the human fus gene with or without mutation. Overexpression of a mutant (R521C substitution), but not normal, human FUS induced progressive paralysis resembling ALS. Mutant FUS transgenic rats developed progressive paralysis secondary to degeneration of motor axons and displayed a substantial loss of neurons in the cortex and hippocampus. This neuronal loss was accompanied by ubiquitin aggregation and …