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Your search keyword '"Carlos A. Pardo-Villamizar"' showing total 5 results
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5 results on '"Carlos A. Pardo-Villamizar"'

1. Identification of the NRF2 transcriptional network as a therapeutic target for trigeminal neuropathic pain

Author

Chirag Vasavda, Risheng Xu, Jason Liew, Ruchita Kothari, Ryan S. Dhindsa, Evan R. Semenza, Bindu D. Paul, Dustin P. Green, Mark F. Sabbagh, Joseph Y. Shin, Wuyang Yang, Adele M. Snowman, Lauren K. Albacarys, Abhay Moghekar, Carlos A. Pardo-Villamizar, Mark Luciano, Judy Huang, Chetan Bettegowda, Shawn G. Kwatra, Xinzhong Dong, Michael Lim, and Solomon H. Snyder

Subjects
Multidisciplinary
Abstract

Trigeminal neuralgia, historically dubbed the “suicide disease,” is an exceedingly painful neurologic condition characterized by sudden episodes of intense facial pain. Unfortunately, the only U.S. Food and Drug Administration (FDA)–approved medication for trigeminal neuralgia carries substantial side effects, with many patients requiring surgery. Here, we identify the NRF2 transcriptional network as a potential therapeutic target. We report that cerebrospinal fluid from patients with trigeminal neuralgia accumulates reactive oxygen species, several of which directly activate the pain-transducing channel TRPA1. Similar to our patient cohort, a mouse model of trigeminal neuropathic pain also exhibits notable oxidative stress. We discover that stimulating the NRF2 antioxidant transcriptional network is as analgesic as inhibiting TRPA1, in part by reversing the underlying oxidative stress. Using a transcriptome-guided drug discovery strategy, we identify two NRF2 network modulators as potential treatments. One of these candidates, exemestane, is already FDA-approved and may thus be a promising alternative treatment for trigeminal neuropathic pain.

Published
2022

2. Granzyme B-induced neurotoxicity is mediated via activation of PAR-1 receptor and Kv1.3 channel.

Author

Tongguang Wang, Myoung-Hwa Lee, Elliot Choi, Carlos A Pardo-Villamizar, Sung Bin Lee, In Hong Yang, Peter A Calabresi, and Avindra Nath

Subjects
Medicine, Science
Abstract

Increasing evidence supports a critical role of T cells in neurodegeneration associated with acute and subacute brain inflammatory disorders. Granzyme B (GrB), released by activated T cells, is a cytotoxic proteinase which may induce perforin-independent neurotoxicity. Here, we studied the mechanism of perforin-independent GrB toxicity by treating primary cultured human neuronal cells with recombinant GrB. GrBactivated the protease-activated receptor (PAR)-1 receptor on the neuronal cell surface leading to decreased intracellular cyclic AMP levels. This was followed by increased expression and translocation of the voltage gated potassium channel, Kv1.3 to the neuronal cell membrane. Similar expression of Kv1.3 was also seen in neurons of the cerebral cortex adjacent to active inflammatory lesions in patients with multiple sclerosis. Kv1.3 expression was followed by activation of Notch-1 resulting in neurotoxicity. Blocking PAR-1, Kv1.3 or Notch-1 activation using specific pharmacological inhibitors or siRNAs prevented GrB-induced neurotoxicity. Furthermore, clofazimine protected against GrB-induced neurotoxicity in rat hippocampus, in vivo. These observations indicate that GrB released from T cells induced neurotoxicity by interacting with the membrane bound Gi-coupled PAR-1 receptor and subsequently activated Kv1.3 and Notch-1. These pathways provide novel targets to treat T cell-mediated neuroinflammatory disorders. Kv1.3 is of particular interest since it is expressed on the cell surface, only under pathological circumstances, and early in the cascade of events making it an attractive therapeutic target.

Published
2012
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3. Pathology and Diagnosis of Central Nervous System Infections

Author

S. K. Shankar, Wong Kum Thong, C Sundaram, and Carlos A. Pardo-Villamizar

Subjects
Pathology, medicine.medical_specialty, Article Subject, business.industry, Cns infections, medicine.medical_treatment, Central nervous system, Immunosuppression, Bioinformatics, medicine.disease, Pathology and Forensic Medicine, Patient management, Editorial, medicine.anatomical_structure, Acquired immunodeficiency syndrome (AIDS), Health care, lcsh:Pathology, Medicine, Disease process, business, Solid organ transplantation, lcsh:RB1-214
Abstract

Infections of the central nervous system (CNS) are important because of the many pathogens, the emerging and reemerging of new infections, and the heavy burden they impose on health care system. The most formidable challenge is the increasing number of people at risk of developing CNS infections due to acquired immunodeficiency syndrome (AIDS) and the recipients of hemopoietic and solid organ transplantation and other causes of immunosuppression. There have been significant developments in the last few decades in understanding the biology of disease process by the application of new technologies. Advancements in brain imaging and newer diagnostic modalities have achieved early diagnosis helping patient management with new therapies. The pathogenetic factors contributing to neurovirulence of the pathogens have been elucidated by the use of molecular biological techniques.

Published
2011
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5. Contributors

Author

Neha P. Amin, Charles E. Argoff, Allen J. Askamit, Alon Y. Avidan, Laura J. Balcer, Tallie Z. Baram, Allan J. Belzberg, Sara E. Benjamin, Anish Bhardwaj, Kevin M. Biglan, Tom J. Blanchard, John B. Bodensteiner, Devin L. Brown, John C.M. Brust, Arthur L. Burnett, Anthony S. Burns, Peter Calabresi, Grant L. Campbell, Vinay Chaudhry, William P. Cheshire, Kenneth Cohen, Andrew J. Cole, Anne Comi, James J. Corbett, Andrea M. Corse, Nathan E. Crone, Ricardo Cruciani, Marinos C. Dalakas, Josep Dalmau, Stephanie K. Daniels, Larry E. Davis, David W. Dodick, Heinrich Elinzano, Robert D. Fealey, Anne L. Foundas, Jacqueline A. French, Linda P. Fried, Scott Fromherz, Bhuwan P. Garg, Donald L. Gilbert, Mark R. Gilbert, Donald H. Gilden, Frank G. Gilliam, Jonathan P. Gladstone, Jonathan D. Glass, David S. Goldstein, Joao A. Gomes, Benjamin M. Greenberg, Adam L. Hartman, Susan T. Herman, Argye E. Hillis, Michio Hirano, David Irani, Sallu Jabati, Alan C. Jackson, Jee-Hyang Jeong, H.A. Jinnah, S. Claiborne Johnston, Burk Jubelt, Douglas Kerr, Richard M. Kimball, Kleopas A. Kleopa, Carol Lee Koski, Eric H. Kossoff, Allan Krumholz, Roger W. Kula, Ralph W. Kuncl, John Laterra, Robert Laureno, Rafael H. Llinás, Elan D. Louis, Yukari Manabe, Nicholas J. Maragakis, Morri E. Markowitz, Christina M. Marra, Laura Marsh, James A. Mastrianni, Justin C. McArthur, Una D. McCann, Micheline McCarthy, Emmanuel Mignot, Bruce Miller, Steven P. Miller, Lewis B. Morgenstern, Richard T. Moxley, Beth Murinson, Neal J. Naff, Vinodh Narayanan, Avindra Nath, Elizabeth O'Hearn, Richard K. Olney, Andrew R. Pachner, Carlos A. Pardo-Villamizar, Roy A. Patchell, Michael Polydefkis, Beth S. Porter, Michael Pourfar, Tyler Reimschisel, George A. Ricaurte, Daniele Rigamonti, Stacie L. Ropka, Paul Rosenberg, Robert L. Ruff, David B. Rye, Steven S. Scherer, Jacob P. Schwarz, Erick Scott, James J. Sejvar, Michael E. Selzer, Jehuda Sepkuty, Barbara E. Shapiro, Rachelle Smith Doody, Yuen T. So, Tom Solomon, Elijah W. Stommel, Gene Sung, Tricia Ting, B. Todd Troost, Eileen P.G. Vining, Jerrold L. Vitek, Kathryn R. Wagner, Mark F. Walker, Laurence Walsh, Benjamin L. Walter, Michael R. Watters, Michael A. Williams, Max Wiznitzer, Wendy L. Wright, Kaleb Yohay, Phyllis C. Zee, Wendy C. Ziai, and Andrew W. Zimmerman

Published
2006
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