A serum microRNA signature for amyotrophic lateral sclersosis reveals convergent RNA processing defects and identifies presymptomatic mutation carriers

This scientific commentary refers to ‘Serum microRNAs in patients with genetic amyotrophic lateral sclerosis and pre-manifest mutation carriers’ by Freischmidt et al. (doi: 10.1093/brain/awu249). Defective RNA processing has occupied centre stage in the pathogenesis of amyotrophic lateral sclerosis (ALS) since the identification of TARDBP (also known as TDP-43) inclusions in 95% of cases and pathogenic mutations in RNA processing genes such as TARDBP , FUS and MATR3 (Sreedharan et al. , 2008; Vance et al. , 2009; Johnson et al. , 2014). FUS and TARDBP are known to regulate mRNA transcription, splicing, stability and transport (Tollervey et al. , 2011; Rogelj et al. , 2012) but they are also part of the large Drosha complex that regulates microRNA (miRNA) biogenesis (Gregory et al. , 2004). Dysregulation of miRNA expression has been shown in many cancers and more recently in Alzheimer’s disease and is predicted to play a mechanistic role and/or be an indirect biomarker of disease.In this issue of Brain , Freischmidt et al. (2014) report that levels of a specific subset of miRNAs are reduced in the serum of patients …