Pharmacological promotion of inclusion formation: A therapeutic approach for Huntington’s and Parkinson’s diseases
| Autor: | Bradley T. Hyman, Ruth A. Bodner, Aleksey G. Kazantsev, Stephanie H. Cho, Stephen M. Altmann, Pamela J. McLean, Tiago F. Outeiro, David E. Housman, Michele M. Maxwell, Anne B. Young |
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| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
Cellular pathology
Proteasome Endopeptidase Complex Protein Folding Huntingtin Recombinant Fusion Proteins Green Fluorescent Proteins DNA Recombinant Nerve Tissue Proteins Disease CHO Cells Biology In Vitro Techniques Bioinformatics Piperazines Cell Line Therapeutic approach Genes Reporter Cricetinae mental disorders Animals Humans Amino Acid Sequence Inclusion Bodies Huntingtin Protein Multidisciplinary Base Sequence Nuclear Proteins Parkinson Disease Biological Sciences Virology nervous system diseases Huntington Disease Proteasome Quinolines alpha-Synuclein |
| Popis: | Misfolded proteins accumulate in many neurodegenerative diseases, including huntingtin in Huntington’s disease and α-synuclein in Parkinson’s disease. The disease-causing proteins can take various conformations and are prone to aggregate and form larger cytoplasmic or nuclear inclusions. One approach to the development of therapeutic intervention for these diseases has been to identify chemical compounds that reduce the size or number of inclusions. We have, however, identified a compound that promotes inclusion formation in cellular models of both Huntington’s disease and Parkinson’s disease. Of particular interest, this compound prevents huntingtin-mediated proteasome dysfunction and reduces α-synuclein-mediated toxicity. These results demonstrate that compounds that increase inclusion formation may actually lessen cellular pathology in both Huntington’s and Parkinson’s diseases, suggesting a therapeutic approach for neurodegenerative diseases caused by protein misfolding. |
| Databáze: | OpenAIRE |
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