Alzheimer's disease (AD) is a chronic disabling disease that affects the central nervous system. The main consequences of ADinclude the decline of cognitive functions and language disorders. One of the causes leading to AD is the decrease of neurotransmitter acetylcholine(ACh) levels in the brain, in part due to a higher activity of acetylcholinesterase (AChE), the enzyme responsible for its degradation. Manyacetylcholinesterase inhibitors (AChEIs), both natural and synthetic, have been developed and used through the years to counteract the progressionof the disease. The first of such drugs approved for a therapeutic use was tacrine, that binds through a reversible bond to the enzyme.However, tacrine has since been withdrawn because of its adverse effects. Currently, donepezil and galantamine are very promising AChEIswith clinical benefits. Moreover, rivastigmine is considered a pseudo-irreversible compound with anti-AChE action, providing similar effects atthe clinical level. The purpose of this review is to provide an overview of what has been published over the last decade on the effectiveness ofAChEIs in AD, analysing the most relevant issues under the clinical and methodological profiles and the consequent possible welfare effects forthe whole world. Furthermore, novel drugs and possible therapeutic approaches are also discussed.

The State of The Art on Acetylcholinesterase Inhibitors in the Treatment of Alzheimer's Disease

Immacolata Vecchio;Annamaria Paoletti;Rosario Marra;Mariamena Arbitrio
2021

Abstract

Alzheimer's disease (AD) is a chronic disabling disease that affects the central nervous system. The main consequences of ADinclude the decline of cognitive functions and language disorders. One of the causes leading to AD is the decrease of neurotransmitter acetylcholine(ACh) levels in the brain, in part due to a higher activity of acetylcholinesterase (AChE), the enzyme responsible for its degradation. Manyacetylcholinesterase inhibitors (AChEIs), both natural and synthetic, have been developed and used through the years to counteract the progressionof the disease. The first of such drugs approved for a therapeutic use was tacrine, that binds through a reversible bond to the enzyme.However, tacrine has since been withdrawn because of its adverse effects. Currently, donepezil and galantamine are very promising AChEIswith clinical benefits. Moreover, rivastigmine is considered a pseudo-irreversible compound with anti-AChE action, providing similar effects atthe clinical level. The purpose of this review is to provide an overview of what has been published over the last decade on the effectiveness ofAChEIs in AD, analysing the most relevant issues under the clinical and methodological profiles and the consequent possible welfare effects forthe whole world. Furthermore, novel drugs and possible therapeutic approaches are also discussed.
2021
Istituto per la Ricerca e l'Innovazione Biomedica -IRIB
Alzheimer's disease
behavioral/cognitive syndromes
acetylcholinesterase's inhibitors
Alzheimer's treatment
disease modifying therapeutics
phase Alzheimer's clinical trials
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14243/399760
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