Change in FUS protein involved in early onset of FTD

Researchers from the department prof. dr. Boris Rogelj, assist. prof. dr. Helena Motaln and young researcher Urša Čerček, together with colleagues from Germany and the Netherlands discovered change in FUS protein involved in early onset of frontotemporal dementia (FTD). By synthesizing and validating a specific detector (antibody) for the modified last amino acid of FUS protein and advanced microscopy, recearchers revealed the distribution pattern of soluble and insoluble FUS protein in cells, which is not detected by commercially available detectors. Researchers confirmed the involvement of SRC family kinases in FUS phosphorylation and examined the level of protein phosphorylation and Abl kinase activity in cortical brain neurons. Under conditions of oxidative stress, they demonstrated the direct involvement of Abl kinase in modified FUS sequestration in toxic aggregates. Success of the study is the identification of a novel role of Abl kinase in the intracellular localization of FUS in neurons, which is critical for the development and progression of FUS-FTLD. Control of this mechanism would improve neuron survival.

Link to the article: 10.1093/brain/awad130
Figure: Differentiated SH-SY5Y cells with nucleus (blue), expressing neural marker SYP (green) and phosphorylated FUS (red)

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