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Published in: NeuroMolecular Medicine 2/2015

01-06-2015 | Original Paper

Unfolding the Promise of Translational Targeting in Neurodegenerative Disease

Author: Thomas M. Drake

Published in: NeuroMolecular Medicine | Issue 2/2015

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Abstract

With the rise of aging populations, new challenges for health care systems are emerging. Degenerative conditions of the central nervous system share a strikingly great deal of similarities, particularly the production and buildup of malfolded proteins. As a result, stress pathways within the endoplasmic reticulum become activated, triggering widespread neuronal apoptosis. New pharmacological compounds targeting this response are emerging as promising treatment strategies. This review examines the current evidence for protein aggregation in neurodegenerative disease states and discusses future mechanisms of therapeutically targeting the endoplasmic reticulum.
Literature
go back to reference Alzheimer Association. (2014). Alzheimer’s disease facts and figures. Alzheimer Association. (2014). Alzheimer’s disease facts and figures.
go back to reference Auluck, P. K., Chan, H. Y. E., & Trojanowski, J. Q. (2002). Chaperone suppression of {alpha}-synuclein toxicity in a drosophila model for Parkinson’s disease. Science, 295(5556), 865–868. Auluck, P. K., Chan, H. Y. E., & Trojanowski, J. Q. (2002). Chaperone suppression of {alpha}-synuclein toxicity in a drosophila model for Parkinson’s disease. Science, 295(5556), 865–868.
go back to reference Investigators, MADE. (2013). Minocycline in Alzheimer’ S disease efficacy trial: The MADE trial. NIHR Protocol, 1–32. Investigators, MADE. (2013). Minocycline in Alzheimer’ S disease efficacy trial: The MADE trial. NIHR Protocol, 1–32.
go back to reference Investigators, Ninds Net-Pd. (2006). A randomized, double-blind, futility clinical trial of creatine and minocycline in early Parkinson disease. Neurology, 66(5). AAN Enterprises: 664–671. Investigators, Ninds Net-Pd. (2006). A randomized, double-blind, futility clinical trial of creatine and minocycline in early Parkinson disease. Neurology, 66(5). AAN Enterprises: 664–671.
go back to reference Korennykh, A. V., Egea, P. F., Korostelev, A. A., Finer-moore, J., Shokat, K. M., Stroud, R. M. & Walter, P. (2010). NIH public access, 457(3), 687–693. doi:10.1038/nature07661.The. Korennykh, A. V., Egea, P. F., Korostelev, A. A., Finer-moore, J., Shokat, K. M., Stroud, R. M. & Walter, P. (2010). NIH public access, 457(3), 687–693. doi:10.​1038/​nature07661.​The.
go back to reference Kosmaczewski, S. G., Edwards, T. J., Han, S. M., Eckwahl, M. J., Meyer, B. I., Peach, S., Hesselberth, J. R., Wolin, S. L., & Hammarlund, M. (2014). The RtcB RNA ligase is an essential component of the metazoan unfolded protein response. EMBO Reports, 15(12), 1278–1285. doi:10.15252/embr.201439531. http://www.ncbi.nlm.nih.gov/pubmed/25366321. Kosmaczewski, S. G., Edwards, T. J., Han, S. M., Eckwahl, M. J., Meyer, B. I., Peach, S., Hesselberth, J. R., Wolin, S. L., & Hammarlund, M. (2014). The RtcB RNA ligase is an essential component of the metazoan unfolded protein response. EMBO Reports, 15(12), 1278–1285. doi:10.15252/embr.201439531. http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​25366321.
go back to reference Luk, K. C., Kehm, V., Carroll, J., Zhang, B., Brien, P. O., Trojanowski, J. Q., & Lee, V. M. (2012). Pathological alpha-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science, 338, 949–954.CrossRefPubMedCentralPubMed Luk, K. C., Kehm, V., Carroll, J., Zhang, B., Brien, P. O., Trojanowski, J. Q., & Lee, V. M. (2012). Pathological alpha-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science, 338, 949–954.CrossRefPubMedCentralPubMed
go back to reference Nakagawa, T., Zhu, H., Morishima, N., & Li, E. (2000). Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta. 403, 8–13. Nakagawa, T., Zhu, H., Morishima, N., & Li, E. (2000). Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta. 403, 8–13.
go back to reference Nunziante, M., Ackermann, K., Dietrich, K., Wolf, H., Gädtke, L., Gilch, S., Vorberg, I., Groschup, M., & Schätzl, H. M. (2011). Proteasomal dysfunction and endoplasmic reticulum stress enhance trafficking of prion protein aggregates through the secretory pathway and increase accumulation of pathologic prion protein. The Journal of Biological Chemistry, 286(39). 9650 Rockville Pike, Bethesda, MD 20814, U.S.A.: American Society for Biochemistry and Molecular Biology: 33942–33953. doi:10.1074/jbc.M111.272617. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3190803/. Nunziante, M., Ackermann, K., Dietrich, K., Wolf, H., Gädtke, L., Gilch, S., Vorberg, I., Groschup, M., & Schätzl, H. M. (2011). Proteasomal dysfunction and endoplasmic reticulum stress enhance trafficking of prion protein aggregates through the secretory pathway and increase accumulation of pathologic prion protein. The Journal of Biological Chemistry, 286(39). 9650 Rockville Pike, Bethesda, MD 20814, U.S.A.: American Society for Biochemistry and Molecular Biology: 33942–33953. doi:10.​1074/​jbc.​M111.​272617. http://​www.​ncbi.​nlm.​nih.​gov/​pmc/​articles/​PMC3190803/​.
go back to reference Sano, M., Thomas, R. G., & Van Dyck, C. H. (2011). Placebo-controlled trial of simvastatin to treat Alzheimer sisease. Sano, M., Thomas, R. G., & Van Dyck, C. H. (2011). Placebo-controlled trial of simvastatin to treat Alzheimer sisease.
go back to reference Ulloa-Aguirre, A., & Conn, P. M. (2012). Pharmacoperones: A new therapeutic approach for diseases caused by misfolded G protein-coupled receptors. Recent Patents on Endocrine, Metabolic & Immune Drug Discovery, 5(1), 13–24.CrossRef Ulloa-Aguirre, A., & Conn, P. M. (2012). Pharmacoperones: A new therapeutic approach for diseases caused by misfolded G protein-coupled receptors. Recent Patents on Endocrine, Metabolic & Immune Drug Discovery, 5(1), 13–24.CrossRef
go back to reference Yan, Y. (2013). Minocycline alleviates beta-amyloid protein and tau pathology via restraining neuroinflammation induced by diabetic metabolic disorder, 1089–1095. Yan, Y. (2013). Minocycline alleviates beta-amyloid protein and tau pathology via restraining neuroinflammation induced by diabetic metabolic disorder, 1089–1095.
Metadata
Title
Unfolding the Promise of Translational Targeting in Neurodegenerative Disease
Author
Thomas M. Drake
Publication date
01-06-2015
Publisher
Springer US
Published in
NeuroMolecular Medicine / Issue 2/2015
Print ISSN: 1535-1084
Electronic ISSN: 1559-1174
DOI
https://doi.org/10.1007/s12017-015-8346-x

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