ALS: astrocytes take center stage, but must they share the spotlight?


Recent research has implicated non-neuronal cells in the degeneration of motor neurons in amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease. In two articles published in Nature Neuroscience, Nagai et al. and Di Giorgio et al. present in vitro data that link astrocytes to motor neuron cell death in cellular models of ALS initiated by mutant Cu/Zn2þ superoxide dismutase 1 (SOD1). Furthermore, the results indicate that mutant SOD1 astrocytes release one or more toxic substances that selectively kill both mutant and wild-type motor neurons. These discoveries signal new directions for ALS research and the search for effective treatments. Amyotrophic lateral sclerosis is a progressive neurodegenerative disease characterized by the selective degeneration of upper and lower motor neurons. Respiratory failure is the most common fatal event, usually occurring 1–5 years after disease onset. The typical age of onset is midlife, ranging from age 45 to 60, with a lifetime risk of 1 in 1000. The mysterious and relentless disease has long frustrated patients and researchers alike. Although the French clinician Jean-Martin Charcot first identified ALS 135 years ago, to this day scientists have been unable to determine the cause or the underlying mechanisms of the sporadic form of the disease, which is the most prevalent manifestation and of unknown etiology. However, we do know that mutations in SOD1 cause one rare form of familial ALS, accounting for approximately 2% of the total cases in humans. Furthermore, most of our knowledge of the pathology of ALS derives from studies of mutant SOD1 animal models. The hope is that studies of these rare familial ALS cases will lead to a better understanding of the mechanisms underlying the more common sporadic disease.

DOI: 10.1038/sj.cdd.4402241

Cite this paper

@article{Knott2007ALSAT, title={ALS: astrocytes take center stage, but must they share the spotlight?}, author={Andrew B. Knott and Ella Bossy-Wetzel}, journal={Cell Death and Differentiation}, year={2007}, volume={14}, pages={1985-1988} }