Advances in the Treatment of Alzheimer’s Disease: Benefits of Dual Cholinesterase Inhibition

Abstract

Cholinesterase inhibitors have produced the best evidence of clinical efficacy for treating patients with Alzheimer’s disease (AD). Many of these drugs selectively inhibit acetylcholinesterase (AChE), but agents that also target butyrylcholinesterase (BuChE) may provide added benefits. As AD progresses, ACh regulation may become increasingly dependent on BuChE and dual inhibitors may provide more sustained efficacy than AChE-selective agents. Dual inhibition may also help to slow the formation of amyloidogenic compounds, providing an important disease-modifying mechanism. Rivastigmine is a dual inhibitor that has demonstrated benefits across the spectrum of AD severity and across the cognitive, functional and behavioural domains of AD. It is a priority for future clinical trials to determine whether agents with dual inhibition properties have greater clinical efficacy.

Equipotent Inhibition of Fatty Acid Amide Hydrolase and Monoacylglycerol Lipase – Dual Targets of the Endocannabinoid System to Protect against Seizure Pathology

“…A single drug targeting more than 1 protective pathway, such as AM6701, provides a unique approach related to the use of combinatorial treatments for different neurodegenerative diseases. For example, the use of inhibitor cocktails in studies of Parkinson's disease [68,69], Alzheimer's disease [70][71][72], and stroke [73,74] appears effective for therapeutic intervention. The additive or synergistic efficacy of a compound such as AM6701 may also help alleviate adverse drug effects by reducing the number of administered agents to target different pathways for precise fine-tuning of cannabinergic signaling.…”

Essential Oil from Lemon Peels Inhibit Key Enzymes Linked to Neurodegenerative Conditions and Pro-oxidant Induced Lipid Peroxidation

“…The dose-dependent inhibition of acetylcholinesterase AChE and butyrylcholinesterase BChE activity by the lemon peel essential oil is of immense importance in the management of neurodegenerative conditions as this increases communication between nerve cells 32 . More so, the butyrylcholinesterase BChE inhibition by the essential oils is also beneficial as BChE increases the neurotoxicity of certain plaques thereby making the brain more susceptible to Alzheimer s disease 33,34 . The anticholinesterase activity of the essential oil could be linked to the phenolic content, as some phenolic rich plant extracts have been shown to inhibit cholinesterases 35 .…”

Role of Cholinesterase Inhibitors in Parkinson’s Disease and dementia with Lewy Bodies

“…In addition, BuChE contributes to breakdown of other neuroactive peptides, and may play an important role in the maturation of senile plaques in AD. 20 What is the clinical relevance of BuChE in PDD and DLB? Genetic polymorphisms associated with reduced BuChE activity were associated with preserved attentional performance and slower rate of cognitive decline in AD and DLB.…”