期刊
HUMAN MOLECULAR GENETICS
卷 20, 期 18, 页码 3545-3553出版社
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddr271
关键词
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资金
- Laboratorios Salvat SA
- Spanish Ministry of Science and Innovation [MICINN-BIO2007-60066, SAF2010 15512, CSD2008-00005C]
- ERDF [2010/005]
- GV
Minocycline (7-dimethylamino-6-dimethyl-6-deoxytetracycline) is a second-generation tetracycline that can cross the blood-brain barrier and has anti-inflammatory and neuroprotective effects. The potential of minocycline as a drug for treating Huntington's disease has been studied; however, the molecular mechanism underlying the neuroprotective properties of minocycline remains elusive. In this study, we tested the hypothesis that a principal cellular target of minocycline is Apaf-1, a key protein in the formation of the apoptosome, a multiprotein complex involved in caspase activation. Minocycline binds to Apaf-1, as shown by nuclear magnetic resonance spectroscopy, and inhibits apoptosome activity in vitro and in ex vivo models. As a consequence, minocycline-treated cells as well as Apaf-1 knock-out cells are resistant to the development of mutant huntingtin-dependent protein aggregation.
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