Neuromuscular diseases: muscleSpinal muscular atrophies reveal motor neuron vulnerability to defects in ribonucleoprotein handlingAnderson, Kirstiea; Talbot, Kevina,bAuthor Information aDepartment of Human Anatomy and Genetics, University of Oxford and bDepartment of Clinical Neurology, Radcliffe Infirmary, Oxford, UK Correspondence to Dr Kevin Talbot, Department of Clinical Neurology, Radcliffe Infirmary, Woodstock Road, Oxford, OX2 6HE, UK E-mail: firstname.lastname@example.org Current Opinion in Neurology: October 2003 - Volume 16 - Issue 5 - p 595-599 Buy Abstract Purpose of review Many forms of spinal muscular atrophy, a pure lower motor neuron disease, have been characterized clinically but the molecular basis of most of these is unknown. In this article we review recent developments in our understanding of the spinal muscular atrophies and how this knowledge has revealed important new insights into the causes of motor neuron vulnerability which may ultimately lead to novel therapies for this untreatable group of disorders. Recent findings The identification of the genetic basis of two forms of autosomal recessive spinal muscular atrophy has revealed that lower motor neurons appear to have a specific vulnerability to defects in RNA metabolism. Most notably, the survival motor neuron protein, deficient in the most common form of spinal muscular atrophy, plays a multifunctional role in ribonucleoprotein metabolism and pre-messenger RNA splicing. The role of this protein in motor neurons is currently under intense study. The identification of two other spinal muscular atrophy-causing genes has provided support for the central role of components of the RNA metabolic pathway in determining motor neuron survival. Summary Understanding the molecular basis of lower motor neuron vulnerability in disorders such as spinal muscular atrophy will ultimately allow these disabling disorders to be treated. In addition we can expect to learn much about basic neuronal biology and about the pathways that are relevant to more common neurodegenerative disorders such as amyotrophic lateral sclerosis. © 2003 Lippincott Williams & Wilkins, Inc.