Galectins are pleiotropic
carbohydrate-binding
lectins involved in
inflammation, growth/differentiation, and tissue remodeling. The functional role of
galectins in
amyotrophic lateral sclerosis (ALS) is unknown. Expression studies revealed increases in
galectin-1 mRNA and
protein in spinal cords from SOD1(G93A) mice, and in
galectin-3 and -9 mRNAs and
proteins in spinal cords of both SOD1(G93A) mice and sporadic ALS patients. As the increase in
galectin-3 appeared in early presymptomatic stages and increased progressively through to end stage of disease in the mouse, it was selected for additional study, where it was found to be mainly expressed by microglia.
Galectin-3 antagonists are not selective and do not readily cross the blood-brain barrier; therefore, we generated SOD1(G93A)/Gal-3(-/-) transgenic mice to evaluate
galectin-3 deletion in a widely used mouse model of ALS.
Disease progression, neurological symptoms, survival, and
inflammation were assessed to determine the effect of
galectin-3 deletion on the SOD1(G93A) disease phenotype.
Galectin-3 deletion did not change disease onset, but resulted in more rapid progression through functionally defined disease stages, more severely impaired neurological symptoms at all stages of disease, and expiration, on average, 25 days earlier than SOD1(G93A)/Gal-3(+/+) cohorts. In addition, microglial staining, as well as TNF-α, and oxidative injury were increased in SOD1(G93A)/Gal-3(-/-) mice compared with SOD1(G93A)/Gal-3(+/+) cohorts. These data support an important functional role for microglial
galectin-3 in
neuroinflammation during chronic
neurodegenerative disease. We suggest that elevations in
galectin-3 by microglia as disease progresses may represent a protective, anti-inflammatory innate immune response to chronic motor neuron degeneration.