Francis PT, Nordberg A, Arnold SE. A preclinical view of cholinesterase inhibitors in neuroprotection: do they provide more than symptomatic benefits in Alzheimer's disease? Trends Pharmacol Sci 26: 104-111

Wolfson Centre for Age-Related Diseases, Guy's Campus, St Thomas Street, Kings College London, London SE1 1UL, UK.
Trends in Pharmacological Sciences (Impact Factor: 11.54). 03/2005; 26(2):104-11. DOI: 10.1016/
Source: PubMed


The prevalence of Alzheimer's disease (AD), a neurodegenerative condition whose greatest risk factor is old age, is expected to rise dramatically during the next five decades, along with the trend for increased longevity. Early diagnosis and intervention with therapies that halt or slow disease progress are likely to represent an important component of effective treatment. Although much progress has been made in this area, there are currently no clinically approved interventions for AD that are classed as disease modifying or neuroprotective. Cholinesterase inhibitors are a drug class used for the symptomatic treatment of AD. Recent evidence from preclinical studies indicates that these agents can attenuate neuronal damage and death from cytotoxic insults, and therefore might affect AD pathogenesis. The mechanisms by which these actions are mediated might or might not be directly related to their primary mode of action.

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    • "AChE induces an apoptotic and necrotic cell death by inducing membrane depolarization and NMDA receptor activation with consequent Ca 2+ influx and modulation of the í µí»¼7 nicotinic acetylcholine receptor in hippocampal cultures. Therefore, AChE has a main role in neurodegeneration and AChEIs could be effective in neuro- protection818283. Increasing expression of splice variants of AChE (R and S) as neuroprotective forms of AChE, with AChEIs, has been effective in preventing the progression of AD. "
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    • "Experiments testing the efficacy of drugs in reversing the transient memory deficits caused by SD could thus provide reliable models in drug-discovery preclinical studies for the treatment of dementia-related cognitive decline. To date, treatments of AD and other dementias rely on the administration of anticholinesterase therapy (e.g., donepezil, rivastigmine, galantamine) or NMDA receptor antagonists (i.e., memantine) whose effects at a symptomatic (cognitive and behavioral) level and as neuroprotective agents are still under debate (Bullock, 2002; Francis et al., 2005). "
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