{"product_id":"tdp-43-in-the-pathogenesis-of-amyotrophic-lateral-sclerosis-als-von-vivek-swarup","title":"TDP-43 in the pathogenesis of amyotrophic lateral sclerosis (ALS)","description":"\u003cp\u003eAmyotrophic 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 ALS symptoms. We propose that TDP-43 deregulation contributes to ALS pathogenesis in part by enhancing NF-kappaB activation, and that NF-kappaB may constitute a therpeutic target for ALS.\u003c\/p\u003e\u003cdiv class=\"aw-variant-hidden-subtitle-div\" id=\"aw-variant-subtitle-9783659135644\"\u003e\u003ch3\u003eStudy and characterization of TDP-43 mutants in the pathogenesis of ALS\u003c\/h3\u003e\u003c\/div\u003e","brand":"Autorenwelt Shop","offers":[{"title":"Softcover - 9783659135644","offer_id":39489836580957,"sku":"9783659135644","price":79.0,"currency_code":"EUR","in_stock":true}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/0940\/0622\/files\/d2afe227-eb8a-46e7-8acd-04f8549d271a.jpg?v=1774675247","url":"https:\/\/shop.autorenwelt.de\/products\/tdp-43-in-the-pathogenesis-of-amyotrophic-lateral-sclerosis-als-von-vivek-swarup","provider":"Autorenwelt Shop","version":"1.0","type":"link"}