One emerging difference between ALS-FUS and FTD-FUS is that only the latter typically involves co-aggregation of the FET proteins EWS and TAF15 along with FUS itself. More than 40 FUS mutations have been identified in ALS.

2023年2月28日 · Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder causing progressive loss of motor neurons. Mutations in Fused in sarcoma (FUS) leading to its cytoplasmic mislocalization cause a subset of ALS. Under stress, mutant FUS localizes to stress granules (SGs)—cytoplasmic condensates composed of RNA and various proteins.

2022年12月14日 · Fused in Sarcoma (FUS) is one of the genes associated with ALS. It causes ALS type 6 when mutated and is found mislocalized to the cytoplasm in the motor neurons of sporadic ALS patients (without FUS mutations). In addition, FUS plays a role in all cellular functions that are impaired in degenerating motor neurons.

2024年4月17日 · Intracellular aggregation of fused in sarcoma (FUS) is associated with the pathogenesis of familial amyotrophic lateral sclerosis (ALS). Under stress, FUS forms liquid droplets via...

The latter is a monocistronic FUS version, where all altFUS methionines are mutated for threonines in a manner synonymous for FUS (Appendix Fig S1 C–E). Thus, the FUS protein sequence is unchanged, but the altFUS sequence does not contain any methionines.

2015年11月18日 · We propose a model in which low-complexity (LC) domains of FUS drive its physiologically reversible assembly into membrane-free, liquid droplet and hydrogel-like structures. ALS/FTD mutations in LC or non-LC domains induce further phase transition into poorly soluble fibrillar hydrogels distinct from conventional amyloids.

The latter are now collectively referred to as FTLD-FUS. In the present study, we investigated the localization of FUS in human and mouse brains. FUS was detected by western blot as an approximately 72 kDa protein in both human and mouse brains.

FUS水平通过一种机制自动调节，其中人FUS在mRNA和蛋白质水平下调内源性FUS。 通过使这种自动调节机制饱和而实现的野生型人FUS表达的增加，产生了快速进行的表型和剂量依赖性致死性。

2018年1月23日 · Using human induced pluripotent stem cell (hiPSCs)-derived motor neurons (MNs), we show that impairment of poly (ADP-ribose) polymerase (PARP)-dependent DNA damage response (DDR) signaling due to...

2020年6月1日 · We find that FUS-ALS mutations induce a widespread loss of function on expression and splicing. Specifically, we find that mutant FUS directly alters intron retention levels in RNA-binding proteins. Moreover, we identify an intron retention event in FUS itself that is associated with its autoregulation.