Abstract
Diseases of polyglutamine expansion, Alzheimers disease and Parkinsons disease are neurodegenerative diseases associated with insoluble protein aggregates and neuronal death. These diseases constitute a group of devastating diseases for which there is currently little treatment. The protein aggregates may be the cause of neuronal death, although there is some controversy as to which form of aggregation (oligomers, polymers or microscopic aggregates) is the most toxic. More than a decade ago, the participation of transglutaminases in the formation of the abnormal protein aggregates was proposed. Transglutaminases are a large family of enzymes that catalyze the formation of Nε(γ-glutamyl)-lysine isodipeptide crosslinks between proteins. In this review, we summarize the evidence supporting the participation of transglutaminase in diseases of the central nervous system. We also describe newly developed transglutaminase inhibitors and their potential use as therapeutic agents in neurological disease.
Keywords: Polyglutamine, Alzheimer, Parkinson, protein aggregation, neuronal inclusions
CNS & Neurological Disorders - Drug Targets
Title: Transglutaminase-Catalyzed Crosslinking in Neurological Disease: From Experimental Evidence to Therapeutic Inhibition
Volume: 9 Issue: 2
Author(s): G. Hoffner, W. Andre, A. Vanhoutteghem, S. Soues and P. Djian
Affiliation:
Keywords: Polyglutamine, Alzheimer, Parkinson, protein aggregation, neuronal inclusions
Abstract: Diseases of polyglutamine expansion, Alzheimers disease and Parkinsons disease are neurodegenerative diseases associated with insoluble protein aggregates and neuronal death. These diseases constitute a group of devastating diseases for which there is currently little treatment. The protein aggregates may be the cause of neuronal death, although there is some controversy as to which form of aggregation (oligomers, polymers or microscopic aggregates) is the most toxic. More than a decade ago, the participation of transglutaminases in the formation of the abnormal protein aggregates was proposed. Transglutaminases are a large family of enzymes that catalyze the formation of Nε(γ-glutamyl)-lysine isodipeptide crosslinks between proteins. In this review, we summarize the evidence supporting the participation of transglutaminase in diseases of the central nervous system. We also describe newly developed transglutaminase inhibitors and their potential use as therapeutic agents in neurological disease.
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Cite this article as:
Hoffner G., Andre W., Vanhoutteghem A., Soues S. and Djian P., Transglutaminase-Catalyzed Crosslinking in Neurological Disease: From Experimental Evidence to Therapeutic Inhibition, CNS & Neurological Disorders - Drug Targets 2010; 9 (2) . https://dx.doi.org/10.2174/187152710791012107
DOI https://dx.doi.org/10.2174/187152710791012107 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
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