Current Drug Targets

Francis J. Castellino
Kleiderer-Pezold Professor of Biochemistry
Director, W.M. Keck Center for Transgene Research
Dean Emeritus, College of Science
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Structural and Functional Studies of Galectin-1: A Novel Axonal Regeneration-Promoting Activity for Oxidized Galectin-1

Author(s): Toshihiko Kadoya and Hidenori Horie

Affiliation: CMC R Laboratories, Pharmaceutical Division, Kirin Brewery Co. Ltd., 100-1 Hagiwara, Takasaki, Gunma 370-0013, Japan.

Abstract:

Recently, we discovered oxidized galectin-1 as a factor that regulates initial axonal growth in the peripheral nerve after axotomy. Galectin-1 is a member of the galectins, a family of animal lectins ranging from Caenorhabditis elegans to humans, which is defined by their affinity for β-galactosides and by significant sequence similarity in the carbohydrate-binding site. Galectin-1 is a homodimer with a subunit molecular mass of 14.5 kDa, which contains six cysteine residues per subunit. The cysteine residues should be in a free state in order to maintain a molecular structure that is capable of showing lectin activity. However, our structural analysis revealed that the axonal regeneration-promoting factor exists as an oxidized form of galectin-1, containing three intramolecular disulfide bonds. The oxidized galectin-1 exhibited marked peripheral nerve regeneration-promoting activity, although it showed no lectin activity. It was also revealed that oxidized galectin-1 exists as a monomer in a physiological solution. Galectin-1 seems to have a variety of biological functions. These functions could vary according to the time at which a biological function is taking place, as well as the site in which a biological function is taking place. In addition, these functions could vary according to the structure of galectin-1 by which a particular biological function is taking place. Disulfide bond formation alters the structure of galectin-1, so as to confer the novel ability to promote axonal regeneration. Oxidized galectin-1 likely acts as an autocrine or paracrine factor to promote axonal regeneration, functioning more like a cytokine than as a lectin.

Keywords: galectin, oxidized galectin, disulfide bond, structure-activity relationship, lectin, axonal regeneration, peripheral nerve injury

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Article Details

VOLUME: 6
ISSUE: 4
Page: [375 - 383]
Pages: 9
DOI: 10.2174/1389450054022007
Price: $58