TDP-43 in the pathogenesis of amyotrophic lateral sclerosis (ALS) Год выпуска: 2012Автор: Vivek SwarupИздательство: LAP Lambert Academic PublishingСтраниц: 324ISBN: 9783659135644Описание Amyotrophic lateral sclerosis (ALS) is a lethal disease characterized by degeneration of lower and upper motor neurons. Transactive response DNA-binding protein 43 (TDP-43) ubiquitinated inclusions are a hallmark of ALS. In order to understand the pathogenic mechanism caused by TDP-43, we generated transgenic mice using genomic fragments encoding human TDP-43 wild-type or FALS-linked mutants TDP-43G348C and TDP-43A315T and used these mice to study the pathogenic mechanism associated with ALS. These novel TDP-43 transgenic mice develop many age-related pathological and biochemical changes reminiscent of human ALS. We also found that TDP-43 interacts with and colocalizes with p65, a NF-kappaB subunit, in glial and neuronal cells from ALS patients. We report that TDP-43 and NF-kappaB p65 mRNA and protein expression is higher in spinal cords of ALS patients than healthy individuals. TDP-43 acted as a co-activator of p65. Treatment of TDP-43 mice with Withaferin A, p65 inhibitor, reduced...
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Ленар, 17.06 Вчера я наконец-то защитился! Оценка Отлично. Большое спасибо за работу. С вами было приятно работать.
