Topic: prion-like mechanism

A key challenge in the study of amyotrophic lateral sclerosis (ALS) is that the affected cells, mainly motor neurons (MNs) and muscle cells (MCs), are difficult to isolate and work with in vitro. In this study, we aimed to investigate the pathological features of ALS using cultured dermal fibroblasts, whose isolation requires a minimally invasive biopsy. [SG1] Morphological and biochemical analyses revealed pronounced cytoplasmic buildup and aggregation of TAR DNA-binding protein 43 (TDP-43) in fibroblasts from ALS patients, reflecting alterations commonly observed in MNs. Moreover, transferri

Huntington Disease (HD) originates from the expansion of a polyglutamine (PolyQ) tract in the Huntingtin protein (Htt), that can assume a Coiled coil fold (Cc). We previously found that Cc structures mediate the aggregation and toxicity of Htt and hypothesize they might be implicated in other aspects of Htt dysfunction. There is evidence that expanded and aggregated Htt can be released by sick cells and taken up by healthy ones. With a prion-like mechanism, aggregated Htt can then seed the misfolding of normal Htt spreading the disorder.We hypothesize that Cc also mediate the intercellular pro