Investigating the molecular basis for selective vulnerability in FET-linked Amyotrophic Lateral Sclerosis (ALS) and Fronto-temporal dementia (FTD)

RNA代谢功能失调已成为神经退行性疾病的共同特征，RNA结合蛋白突变已被确定为几种神经退行性或神经发育障碍的遗传原因（Nussbacher等，2015）。在这些RNA结合蛋白中，融合在肉瘤（FUS）、尤文氏肉瘤（EWS）和TATA-Box结合蛋白相关因子15 （TAF15）是高度保守的多功能核胞质穿梭蛋白，形成了所谓的FET家族（Riggi et al., 2007; Tan and Manley, 2009）。该项目的主要目的是深入了解CNS中FET蛋白在健康衰老过程中的细胞类型特异性表达，以及患者组织中FET相关额颞叶痴呆的背景。这些相互关联的目标可以总结如下。使用显微镜对年轻和年老小鼠大脑和脊髓中FET蛋白表达的时空分析。利用RT-qPCR技术对青年和老年小鼠脑和脊髓中FET基因表达的时空分析

Dysfunctional RNA metabolism has emerged as a common characteristic in neurodegeneration with mutated RNA binding proteins having been identified as the genetic cause of several neurodegenerative or neurodevelopmental disorders (Nussbacher et al., 2015). Among these RNA binding proteins are Fused in Sarcoma (FUS), Ewing Sarcoma (EWS), and TATA-Box Binding Protein Associated Factor 15 (TAF15), which are highly conserved multifunctional nucleocytoplasmic shuttling proteins that form the so-called FET family (Riggi et al., 2007; Tan and Manley, 2009). The main aims of this project are to gain insight into the cell type specific expression of the FET proteins in the CNS throughout ageing in health and in the context of FET-linked Frontotemporal Dementia in patient tissue. These interlinked aims can be summarised as follows. Temporospatial analysis of FET protein expression throughout the brain and spinal cord of young and aged mice using microscopy. Temporospatial analysis of FET gene expression throughout the brain and spinal cord of young and aged mice using RT-qPCR Comparative analysis of FET protein expression in human control and ALS/FTD vulnerable and resistant patient tissue.