Astrocytes are known contributors to ALS pathology through non cell-autonomous mechanisms, but whether they act primarily through loss of supportive functions or secretion of toxic factors is still a matter of debate (see Oct 2011 news, Nov 2014 news, Jul 2015 news). A report in the October 15 Frontiers in Cellular Neuroscience provides evidence in support of the former hypothesis. Researchers led by co-senior authors Janine Kirby and Pamela Shaw at the Sheffield Institute for Translational Neuroscience in the UK examined gene expression in isolated astrocytes from mutant SOD1 (mSOD1)-expressing mice at symptomatic and late stages of disease. As disease progressed, astrocytes shifted into an activated state and ramped up activity of lysosomal and phagocytic pathways, possibly to dispose of cellular waste from degenerating neurons. Late-stage astrocytes also exhibited disrupted expression of genes involved in cholesterol homeostasis, possible due to increased phagocytosis of neuronal debris. Now the researchers are aiming to identify meaningful interventions to restore astrocyte function.
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Baker, D, Blackburn, D, Keatinge M, Sokhi, Viskaitis P, Heath P, Ferraiuolo L, Kirby, J, Shaw, P. Lysosomal and phagocytic activity is increased in astrocytes during disease progression in the SOD1 G93A mouse model of amyotrophic lateral sclerosis. Front. Cell. Neurosci. 16 October 2015. [Full Text]