S100A6 overexpression within astrocytes associated with impaired axons from both ALS mouse model and human patients.
Astrogliosis is one of the earliest pathological changes observed in neurodegenerative diseases in general and in amyotrophic lateral sclerosis (ALS) in particular. ALS is characterized by selective degeneration of motoneurons. There are 2 forms of the disease: sporadic ALS (SALS), comprising 90%-95% of cases, and familial ALS (FALS), comprising 5%-10% of cases. FALS is an age-dependent autosomal dominant disorder in which mutations in the homodimeric enzyme Cu/ Zn superoxide dismutase 1 (SOD1) is linked to the disease. The animal model for this disease is a transgenic mouse expressing the mutated human SOD1(G93A) gene. Here we show by immunohistochemistry and double immunofluorescence that astrocytes located near impaired axons of motoneurons that were selectively programmed to die overexpressed S100A6, a Ca2+/Zn2+ binding protein able to translocate into the nucleus. Transgenic mice overexpressing the mutated human SOD1 gene and patients suffering from SALS showed this selective astrocytic S100A6 expression. For instance, the pyramidal tract could be macroscopically detected on S100A6-labeled spinal cord and brainstem sections from SALS patients. Transgenic mice overexpressing the non-mutated SOD1 gene did not overexpress S100A6, although glial fibrillary associated protein astrogliosis was seen. Although these results do not give any clue about the beneficial or detrimental role played by S100A6, its induction may be assumed to appropriately serve some function(s).
Hoyaux
Daphné
D
Laboratory of Histopathology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium.
Boom
Alain
A
Van den Bosch
Ludo
L
Belot
Nathalie
N
Martin
Jean-Jacques
JJ
Heizmann
Claus W
CW
Kiss
Robert
R
Pochet
Roland
R
D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001369:Axons / Q000473:pathology*; D018797:Cell Cycle Proteins; D002490:Central Nervous System / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D008875:Middle Aged; D009046:Motor Neurons / Q000473:pathology*; D009154:Mutation; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1
D018797:Cell Cycle Proteins; D005904:Glial Fibrillary Acidic Protein; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins; C489134:S100a6 protein, mouse; C000606290:SOD1 protein, human; C055351:S100A6 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1