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Lutein is a bioactive found in dark leafy vegetables that may be used as a nutraceutical agent in foodstuff and an inhibitor of key enzymes of the human body such as those involved in the cholinergic system. However, its high hydrophobicity leads to low bioavailability and must be overcome if lutein is to be added in foods. The objective of this study was to evaluate the influence of nanoencapsulated lutein in the activity of the acetylcholinesterase enzyme. The in vitro study was carried out using water in order to evaluate the impact of encapsulation on the hydrophilicity of lutein. In vitro assays showed that lutein, both free and nanoencapsulated, presented a mixed-type inhibition behavior, and encapsulated lutein was able to inhibit acetylcholinesterase activity even in an aqueous medium. Inhibition was also showed by the in silico docking results which show that lutein interacted with the pocket region of the enzyme., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Alzheimer's disease is one of the leading causes of dementia today. This neurodegenerative disorder results in the progressive decline of cognitive ability and memory. The biochemical processes that characterize this disease include the formation of β-amyloid plaques, the development of neurofibrillary tangles, and the loss of cholinergic neurons in the cerebral cortex. In fact, most of the drugs available to deal with this disease are directed at the affectations suffered by diseased individuals in the cholinergic synapse of the Central Nervous System. It is for this reason that the development of drugs directed to therapeutic targets that allow increasing the availability of acetylcholine in the cholinergic synapse is a field of research of great interest. However, success in the clinical use of these compounds is limited by the side effects they produce and by the multifactorial nature of this disease. The present review aims to provide an overview of the cholinergic dysfunction observed in Alzheimer's disease patients that supports the cholinergic hypothesis in its pathophysiology. In addition, cholinesterase activity inhibitors of clinical and innovative use are discussed as an alternative symptomatic therapy for Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Acetylcholinesterase/Butyrylcholinesterase inhibitors are considered an effective method for treating Alzheimer's disease (AD). In this current work, we have computationally analyzed 11 new small molecule drugs used in various neurological diseases and Donepezil, a known inhibitor of acetylcholinesterase, as a positive control. We investigated these drugs for possible fundamental interactions with acetylcholinesterase and butyrylcholinesterase as both are critical in the pathophysiology of Alzheimer's disease. We have selected FDA approved compounds for repurposing as possible inhibitors of these enzymes and novel therapeutic option for Alzheimer's disease. We selected the top two molecules for each protein for their binding energies, interactions, and Donepezil, the most commonly used drug for AD treatment. Molecular simulation and dynamics studies of the top 2 drugs in each case and free energy analysis helped us reach further conclusions about the best possible drugs for repurposing. Brexipirazole and Deutetrabenazine produce encouraging results as butyrylcholinesterase and acetylcholinesterase inhibitors, respectively. [ABSTRACT FROM AUTHOR]

The 'cholinergic hypothesis', based on the correlation of the reduction of cholinergic activity in Alzheimer's disease (AD) with cognition and memory, is currently the most widely-held view for AD. Drug treatments for AD focus mainly on inhibition of acetylcholinesterase (AChE), and to some extent butyrylcholinesterase (BChE). In addition to changes in AChE in AD, there is a rise in the level of the sister enzyme BChE. However, the role of the two cholinesterases is poorly understood in vivo. We characterized several proteins immunohistochemically in brain sections from AChE nullizygote (AChE-/-) and wild type AChE+/+ mice. Previous studies had shown that AChE-/- mouse tissues are devoid of AChE activity and that the overall cholinesterase activity is significantly decreased in the knockout group [16]. Despite the differences of cholinesterase activity, we found no significant structural alterations between the experimental groups. Immunohistochemical examination revealed no neuronal, dendritic, astrocytic, synaptic, microglial, and endothelial differences between AChE-/- and AChE+/+ mice. Similarly, the histochemical examination showed no morphologic alterations between AChE-/- and AChE+/+ mice. Our studies show that neither the absence of AChE nor the presence exclusively of BChE is associated with neuroglial and vascular pathology. [ABSTRACT FROM AUTHOR]

Presents a study which discussed the symptomatic effect of donepezil, rivastigmine, galantamine and memantine on cognitive deficits in the APP23 model. Definition of Alzheimer's disease; Effect of the treatment in the wild-type animals; Results of the study.

Summary. The cholinergic hypothesis of Alzheimer's disease (AD) states 1. that cholinergic neurons in the basal forebrain are severely affected in the course of disease, detectable both histopathologically by a loss of neurons and neurochemically, by a loss of marker enzymes for acetylcholine synthesis and degradation, and 2. that the resulting cerebral cholinergic deficit leads to memory loss and other cognitive and non-cognitive symptoms, which are characteristic for the illness. This hypothesis was mainly based on studies, which had been conducted on brains of patients with advanced dementia. Nevertheless, it has served as the rationale for the development of drugs, i.e. acetylcholine-esterase inhibitors (AChE-I), which have shown consistent, but modest clinical efficacy against cognitive decline and behavioural symptoms of dementia for a limited period of time. These drugs are presently regarded the standard treatment of dementia in Alzheimer's disease. Now, due to a more sensitive and reliable clinical diagnosis, neurobiological investigations can be performed on early stages of disease, when the changes detected presumably are more relevant for the pathogenesis. New studies on the pathophysiology of the cholinergic system in AD suggest 1. that the cholinergic deficit occurs only late in the disease, 2. that at the earliest stages there even is an upregulation of cholinergic activity in the brain, and 3. that an increased activity of AChE may develop under therapy with AChE-I's. These data show that there is a plasticity of the central cholinergic system in AD and that the positive clinical effects of AChE-I are to be weighted against possible detrimental effects on a pathophysiological level. These data challenge the cholinergic hypothesis in its present form, e.g. should stimulate studies on the underlying process, which leads the cholinergic system to increase its activity in patients in the early stage of AD and may have clinical consequences regarding cholinergic drug therapy. [ABSTRACT FROM AUTHOR]