Get access

RNA quality control and protein aggregates in amyotrophic lateral sclerosis: A review


Department of Neurology, University of Miami Miller School of Medicine, Clinical Research Building, 1120 NW 14 Street, Suite 1317, Miami, Florida 33136, USA. E-mail:


Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease in adults. The biologic basis of ALS remains unknown. However, ALS research has taken a dramatic turn over the past 4 years. Ground breaking discoveries of mutations of genes that encode RNA processing proteins, and demonstration that abnormal aggregates of these and other proteins precede motor neuron loss in familial and sporadic ALS, have initiated a paradigm shift in understanding the pathogenic mechanisms of ALS. Curiously, some of these RNA binding proteins have prion-like domains, with a propensity to self-aggregation. The emerging hypothesis that a focal cascade of toxic protein aggregates, and their consequent non–cell-autonomous spread to neighborhood groups of neurons, fits the classical temporo-spatial progression of ALS. This article reviews the current research efforts toward understanding the role of RNA-processing regulation and protein aggregates in ALS. Muscle Nerve 47:330-338, 2013