Galectin-1 is a component of neurofilamentous lesions in sporadic and familial amyotrophic lateral sclerosis

In amyotrophic lateral sclerosis (ALS), abnormal accumulation of neurofilam ents induces pathological changes such as axonal spheroids, cord-like neuri te swellings, and perikaryal conglomerate inclusions in degenerating motor neurons of the spinal cord, and the accumulation seems to cause motor neuro n degeneration in this disease. Such ALS lesions were intensely labeled wit h HepSS-1, a monoclonal antibody to heparan sulfate. Since the identificati on of HepSS-1 immunoreactive substance seems to be an important step for un derstanding the molecular pathology of ALS, we purified the substance from human spinal cord tissue to homogeneity. Amino acid sequence of the protein was consistent with that of galectin-1. Immunohistochemistry using antibod ies against recombinant human galectin-1 showed that galectin-1 was accumul ated in these lesions in ALS. Although HepSS-1 was believed to be specific for heparan sulfate, it reacted with recombinant human galectin-1 which has no heparan sulfate moiety. The results show that galectin-1 is a component of the neurofilamentous lesions in ALS. Since galectin-1 has axonal regene ration-enhancing activity, the abnormal accumulation of galectin-1 to the l esions seems to be related to the pathological process of ALS. (C) 2001 Aca demic Press.