Neurotoxins and neurotoxic species implicated in neurodegeneration.
Neurotoxins, in the general sense, represent novel chemical structures which when administered in vivo or in vitro, are capable of producing neuronal damage or neurodegeneration--with some degree of specificity relating to neuronal phenotype or populations of neurons with specific characteristics (i.e., receptor type, ion channel type, astrocyte-dependence, etc.). The broader term 'neurotoxin' includes this categorization but extends the term to include intra- or extracellular mediators involved in the neurodegenerative event, including necrotic and apoptotic factors. Moreover, as it is recognized that astrocytes are essential supportive satellite cells for neurons, and because damage to these cells ultimately affects neuronal function, the term 'neurotoxin' might reasonably be extended to include those chemical species which also adversely affect astrocytes. This review is intended to highlight developments that have occurred in the field of 'neurotoxins' during the past 5 years, including MPTP/MPP+, 6-hydroxydopamine (6-OHDA), methamphetamine; salsolinol; leukoaminochrome-o-semiquinone; rotenone; iron; paraquat; HPP+; veratridine; soman; glutamate; kainate; 3-nitropropionic acid; peroxynitrite anion; and metals (copper, manganese, lead, mercury). Neurotoxins represent tools to help elucidate intra- and extra-cellular processes involved in neuronal necrosis and apoptosis, so that drugs can be developed towards targets that interrupt the processes leading towards neuronal death.
Segura Aguilar
Juan
J
Molecular and Clinical Pharmacology, ICBM, Faculty of Medicine, University of Chile, Casilla 70000, Santiago, Chile. jsegura@med.uchile.cl
Kostrzewa
Richard M
RM
D000818:Animals; D006801:Humans; D019636:Neurodegenerative Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology