Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis (Nat Neurosci, 2008, 11:251-253)

報告日期: 2008/06/13
報告時間: 17:10/18:00
報告學生: 翁菁憶
講評老師: 莊季瑛
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Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis

 

Nature neuroscience, 11, 251-253, 2008

 

SpeakerChing-Yi Weng (翁菁憶)

CommentatorJih-Ing Chuang, ph.D. (莊季瑛 老師)

Time2008/6/13 17:10-18:00

PlaceRoom 602

 

Abstract

Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease that selectively kills upper and lower motor neuron. Dominant mutations in the gene encoding the ubiquitously expressed superoxide dismutase (SOD1) are the most prominent known cause of inherited ALS. Previously, the authors demonstrate that mutant SOD1-derived damage in microglia accelerates later disease progression (1). To understand that importance role of SOD1 mutant action in astrocytes function in disease. The authors used SOD1G37R mice carrying a deletable mutant SOD1 gene by the Cre recombinase. Authors found that reduction of SOD1G37R in astrocytes sharply slow later disease progression, but did not slowed disease onset nor early disease. However, postnatal reduction of SOD1G37R in motor neurons significantly slowed disease onset. They have also found selective downregulation of mutant SOD1 in astrocytes significantly delayed microglial activation. Diminishing microglial activation inhibited iNOS induction in astrocytes, as well as did not affect disease-dependent loss of EAAT2 glutamate transporter, indicating that a reduction in glutamate transport reflects non–cell autonomous damage to astrocytes. Overall, the authors demonstrate that initial damage within motor neurons induced mutant SOD1-mediated toxicity formation from damaged motor neuron or astrocytes, cause abnormal activation of mutant-expressing microglia, producing high levels of nitric oxide through upregulation of inducible NOS together with secretion of toxic cytokines to motor neurons. A combination of damage from mutant microglia and astrocytes cause further damage to motor neurons, and drive rapid disease progression.

 

Reference

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   their nonneuronal neighbors. Neuron 52:39-59 (2006)

3.     Pasinelli P, Brown RH., Molecular biology of amyotrophic lateral sclerosis:  

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