The Neurotoxic Effects of Ricinus communis Agglutinin-II

Abstract

Toxic lectins, such as ricin, are the state-of-the-art tool in neurobiology for selectively destroying neuronal populations. Strikingly, lectins from plants and the toxins from some pathogenic bacteria that produce enteric and renal diseases share many functional and structural properties. These toxins might mimic the endocytic pathways of constitutive proteins of the organism to gain access to and destroy the metabolic machinery of the cell. In the nervous system, lectins can be applied both peripherally and centrally. Lectins are internalized in axon terminals by receptormediated 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 irreversibly with the synthesis of proteins by catalytically inactivating the 60S eukaryotic ribosome subunit in such an efficient manner that a single molecule of ricin is enough to kill a cell. Therefore, it is possible to discriminate between the effects of selectively destroying a group of cells and the side-effects caused by other lesioning methods such as axotomy or electrocoagulation.

Ricin, as opposed to other lectins, seems to be completely ineffective within the central nervous system. Its effects, when injected into skeletal muscles or peripheral nerves, have been suggested to mimic the syndrome of human motor neuron 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 on central nervous system premotor neurons of the loss of their neuronal target during the execution of well defined motor tasks. In this regard, the oculomotor system is an ideal model, since the normative morphophysiological and behavioral data are already well known. This approach enables precise determination of the fate of target-deprived neurons in an attempt at exploring the regenerative and compensatory capabilities of the brain.