THE NEUROTOXIC EFFECTS OF RICINUS-COMMUNIS AGGLUTININ-II

Toxic lectins, such as ricin, are the state-of-the-art tool in neurobi ology for selectively destroying neuronal populations. Strikingly, lec tins from plants and the toxins from some pathogenic bacteria that pro duce enteric and renal diseases share many functional and structural p roperties. These toxins might mimic the endocytic pathways of constitu tive proteins of the organism to gain access to and destroy the metabo lic machinery of the cell. In the nervous system, lectins can be appli ed both peripherally and centrally. Lectins are internalized in axon t erminals by receptor-mediated endocytosis and transported towards the soma using anterograde and/or retrograde transport pathways. Ricin is the toxic lectin of Ricinus communis. It has been shown to interfere i rreversibly with the synthesis of proteins by catalytically inactivati ng the 60S eukaryotic ribosome subunit in such an efficient manner tha t a single molecule of ricin is enough to kill a cell. Therefore, it i s possible to discriminate between the effects of selectively destroyi ng a group of cells and the side-effects caused by other lesioning met hods such as axotomy or electrocoagulation. Ricin, as opposed to other lectins, seems to be completely ineffective within the central nervou s system. Its effects, when injected into skeletal muscles or peripher al nerves, have been suggested to mimic the syndrome of human motor ne uron disease since it affects only motoneurons and sensory neurons but not surrounding afferents or glia. Finally, a less exploited approach is the use of ricin for the study of the physiological consequences o n central nervous system premotor neurons of the loss of their neurona l target during the execution of well defined motor tasks. In this reg ard, the oculomotor system is an ideal model, since the normative morp hophysiological and behavioral data are already well known. This appro ach enables precise determination of the fate of target-deprived neuro ns in an attempt at exploring the regenerative and compensatory capabi lities of the brain.