Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that is incurable. The disease is characterized by the selective degeneration of upper motor neurons in the motor cortex as well as the lower motor neurons in the brainstem and spinal cord. The cause of ALS remains unknown in 90% of cases, which are referred to as sporadic ALS because there is no family history for the disease.
Cumulative evidence suggests that sporadic ALS may result from complex interactions between genetic susceptibility and aging. The remaining 10% of ALS cases are hereditary and linked to mutations in one of more than 30 distinct genes involved in different cellular processes. There are severe early onset and juvenile cases, the majority of which are caused by mutations in the FUS gene.
FUS is a protein widely expressed across tissues and has a role in various DNA and RNA processing steps, including DNA repair, transcription, RNA splicing, and nucleo-cytoplasmic RNA shuttling. However, mutations in this protein particularly affect motor neurons in ALS. Professor Dr.
David Vilchez and his team at the University of Cologne's CECAD Cluster of Excellence for Aging Research identified two proteins interacting with an ALS-causing mutant FUS variant (FUS P525L) by investigating motor neurons derived from human induced pluripotent stem cells (iPSC). Their results indicate that inhibiting those interacting proteins could be a possible therapeutic target for familial cases caused by mutations in FU.