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Identification and Characterization of TRO19622 (4-Cholesten-3-one, Oxime), a novel compound for the treatment Amyotrophic Lateral Sclerosisстатья
Статья опубликована в высокорейтинговом журнале
Статья опубликована в журнале из списка Web of Science и/или ScopusДата последнего поиска статьи во внешних источниках: 8 июня 2022 г.
- Авторы: Bordet T., Buisson B., Michaud M., Steidl E., Akentieva N., Evers A., Massaad C., Schumacher M., Ostuni M.A., Lacapère J.J., Galea P., Drouot C., Maux D., Henderson C.E., Pruss R.
- Журнал: Journal of Pharmacology and Experimental Therapeutics
- Том: 322
- Номер: 2
- Год издания: 2007
- Издательство: American Society for Pharmacology and Experimental Therapeutics
- Местоположение издательства: United States
- Первая страница: 709
- Последняя страница: 720
- DOI: 10.1124/jpet.107.123000
- Аннотация: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive death of cortical and spinal motor neurons, for which there is no effective treatment. Using a cell-based assay for compounds capable of preventing motor neuron cell death in vitro, a collection of approximately 40,000 low-molecular-weight compounds was screened to identify potential small-molecule therapeutics. We report the identification of cholest-4-en-3-one, oxime (TRO19622) as a potential drug candidate for the treatment of ALS. In vitro, TRO19622 promoted motor neuron survival in the absence of trophic support in a dose-dependent manner. In vivo, TRO19622 rescued motor neurons from axotomy-induced cell death in neonatal rats and promoted nerve regeneration following sciatic nerve crush in mice. In SOD1G93A transgenic mice, a model of familial ALS, TRO19622 treatment improved motor performance, delayed the onset of the clinical disease, and extended survival. TRO19622 bound directly to two components of the mitochondrial permeability transition pore: the voltage-dependent anion channel and the translocator protein 18 kDa (or peripheral benzodiazepine receptor), suggesting a potential mechanism for its neuroprotective activity. TRO19622 may have therapeutic potential for ALS and other motor neuron and neurodegenerative diseases.
- Добавил в систему: Акентьева Наталья Павловна