Indicators of neuroprotection with galantamine

Alzheimer's disease is pathologically characterized by neurofibrillary tangles and beta-amyloid plaques. These observations form the basis for a large number of disease-modifying therapeutic approaches, which might ultimately lead to neuroprotection and enhanced survival of neurons. Recent data suggest a role for cholinergic stimulation, especially the alpha7 nicotinic acetylcholine receptors (nAChR), in beta-amyloid-mediated neurotoxicity. As galantamine is a modest acetylcholinesterase inhibitor in addition to being an allosteric modulator of nicotinic acetylcholine receptors, it is interesting to study the clinical effects of this compound in the light of its neurochemical properties to discern potential neuroprotective effects. The review presents the preclinical evidence in Alzheimer-related models of neuroprotection with galantamine, especially in models related to glutamate and beta-amyloid toxicity in vitro and to cholinergic stress in vivo. There is substantial evidence that these effects occur by upregulation of the protective protein bcl-2 and are mediated via alpha7 nicotinic acetylcholine receptors. The review also identifies possible clinical indicators, such as long-term studies, suggesting a neuroprotective effect for galantamine mediated by alpha7 nicotinic receptors. These clinically relevant neuroprotective properties of galantamine are worthwhile exploring further and their clinical relevance may improve the development of new disease-modifying agents. (C) 2004 Elsevier Inc. All rights reserved.