Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Acetylcholinesterase Inhibition in Neurogenesis, Neuroinflammation and Neurodegeneration Processes

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 24587

Share This Special Issue

Special Issue Editor

Prof. Victoria Clos Guillén

E-Mail Website
Guest Editor

Universitat Autònoma de Barcelona, Barcelona, Spain

Special Issue Information

Dear Colleagues,

The main goal of the Special Issue on “Acetylcholinesterase inhibition in Neurogenesis, Neuroinflammation and Neurodegeneration Processes” is to publish the best contributions on the role of acetylcholinesterase and its inhibition in neurodegenerative processes in the central nervous system (CNS). Review articles, commentaries, and experimental papers are welcome.

Acetylcholinesterase (AChE) is the enzyme responsible for finalizing cholinergic activity in the synaptic cleft, and it is known that in the CNS, cholinergic neurons are involved in multiple processes such as memory and learning, among others. Thus, inhibition of acetylcholinesterase activity is the current treatment of Alzheimer’s disease, in addition to memantine.

However, AChE has also been assigned noncholinergic roles, such as induction of beta amyloid protein aggregation, pro-apoptotic activity, interaction with presenilin-1, etc. In this way, acetylcholinesterase inhibitors (AChEI) have been related to an increase in neurogenesis, neuroplasticity, and also to a decrease in beta amyloid protein aggregation. More recently, different reports have highlighted the interest of the anti-inflammatory cholinergic pathway, especially in neurodegenerative diseases. The increased availability of acetylcholine and its interaction especially with alpha7 nicotinic receptors located in glial cells decreases the inflammation in the brain as described with different anticholinesterasic drugs (galantamine, donepezil).

Consequently, the further insight of both cholinergic and noncholinergic roles of AChE as well as its inhibition in processes such as neurogenesis, neuroinflammation, and neurodegeneration can contribute to new therapeutic approaches, especially for neurodegenerative diseases.

Prof. Victoria Clos Guillén
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

cholinergic neurotransmission
neurogenesis
AChE
acetylcholinesterase
AChEI
acetylcholinesterase inhibitors
neurodegenerative disease
AD
Alzheimer’s disease
Aβ
amyloid β-protein
anti-inflammatory cholinergic pathway
neuroinflammation

Published Papers (5 papers)

Download All Papers

Research

Jump to: Review

13 pages, 1221 KiB

Open AccessArticle

Influence of Acetylcholine Esterase Inhibitors and Memantine, Clinically Approved for Alzheimer’s Dementia Treatment, on Intestinal Properties of the Mouse

by Vu Thu Thuy Nguyen, Jason Sallbach, Malena dos Santos Guilherme and Kristina Endres

Int. J. Mol. Sci. 2021, 22(3), 1015; https://doi.org/10.3390/ijms22031015 - 20 Jan 2021

Cited by 10 | Viewed by 3273

Abstract

Four drugs are currently approved for the treatment of Alzheimer’s disease (AD) by the FDA. Three of these drugs—donepezil, rivastigmine, and galantamine—belong to the class of acetylcholine esterase inhibitors. Memantine, a NMDA receptor antagonist, represents the fourth and a combination of donepezil and memantine the fifth treatment option. Recently, the gut and its habitants, its microbiome, came into focus of AD research and added another important factor to therapeutic considerations. While the first data provide evidence that AD patients might carry an altered microbiome, the influence of administered drugs on gut properties and commensals have been largely ignored so far. However, the occurrence of digestive side effects with these drugs and the knowledge that cholinergic transmission is crucial for several gut functions enforces the question if, and how, this medication influences the gastrointestinal system and its microbial stocking. Here, we investigated aspects such as microbial viability, colonic propulsion, and properties of enteric neurons, affected by assumed intestinal concentration of the four drugs using the mouse as a model organism. All ex vivo administered drugs revealed no direct effect on fecal bacteria viability and only a high dosage of memantine resulted in reduced biofilm formation of E. coli. Memantine was additionally the only compound that elevated calcium influx in enteric neurons, while all acetylcholine esterase inhibitors significantly reduced esterase activity in colonic tissue specimen and prolonged propulsion time. Both, acetylcholine esterase inhibitors and memantine, had no effect on general viability and neurite outgrowth of enteric neurons. In sum, our findings indicate that all AD symptomatic drugs have the potential to affect distinct intestinal functions and with this—directly or indirectly—microbial commensals. Full article

(This article belongs to the Special Issue Acetylcholinesterase Inhibition in Neurogenesis, Neuroinflammation and Neurodegeneration Processes)

► Show Figures

Figure 1

17 pages, 3741 KiB

Open AccessArticle

Neuroprotective Effect of Cudrania tricuspidata Fruit Extracts on Scopolamine-Induced Learning and Memory Impairment

by Seung-Cheol Jee, Kwang Min Lee, Min Kim, Yoo-Jung Lee, Soee Kim, Joon-Oh Park and Jung-Suk Sung

Int. J. Mol. Sci. 2020, 21(23), 9202; https://doi.org/10.3390/ijms21239202 - 2 Dec 2020

Cited by 6 | Viewed by 3077

Abstract

Cudrania tricuspidata has diverse biological activities, such as antioxidant, anti-inflammatory, anticancer, and neuroprotective effects. This study investigated the protective effects of C. tricuspidata fruit extracts (CTFE) against scopolamine (SCO)-induced neuron impairment. The neuroprotective effects of CTFE on SCO-induced memory dysfunction were confirmed in mice using the Barnes maze test. The results showed that co-treatment of SCO and CTFE increased the stay time in the target zone compared with SCO treatment alone. Similarly, the results obtained by the fear conditioning test revealed that SCO-CTFE co-treatment induced the freezing action time under both the contextual fear condition and the cued fear condition compared with SCO treatment alone. Moreover, we showed that CTFE reduced the SCO-induced acetylcholinesterase (AChE) activity, thereby increasing the acetylcholine concentration in mice hippocampal tissues. Consistent with the improvement of memory and recognition function in vivo, our in vitro results showed that CTFE induced cAMP response element binding protein (CREB) and extracellular regulated kinase 1/2 (ERK1/2) activity in PC12 cells and reduced SCO-induced AChE activity. In addition, the microarray results of the hippocampal tissue support our data showing that CTFE affects gene expressions associated with neurogenesis and neuronal cell differentiation markers such as spp1 and klk6. Overall, CTFE exerts a neuroprotective effect via regulation of the CREB and ERK1/2 signaling pathways and could be a therapeutic candidate for neurodegenerative diseases. Full article

(This article belongs to the Special Issue Acetylcholinesterase Inhibition in Neurogenesis, Neuroinflammation and Neurodegeneration Processes)

► Show Figures

Figure 1

20 pages, 3176 KiB

Open AccessCommunication

Acetylcholinesterase Inhibition of Diversely Functionalized Quinolinones for Alzheimer’s Disease Therapy

by Óscar M. Bautista-Aguilera, Lhassane Ismaili, Mourad Chioua, Rudolf Andrys, Monika Schmidt, Petr Bzonek, María Ángeles Martínez-Grau, Christopher D. Beadle, Tatiana Vetman, Francisco López-Muñoz, Isabel Iriepa, Bernard Refouvelet, Kamil Musilek and José Marco-Contelles

Int. J. Mol. Sci. 2020, 21(11), 3913; https://doi.org/10.3390/ijms21113913 - 30 May 2020

Cited by 6 | Viewed by 2569

Abstract

In this communication, we report the synthesis and cholinesterase (ChE)/monoamine oxidase (MAO) inhibition of 19 quinolinones (QN1-19) and 13 dihydroquinolinones (DQN1-13) designed as potential multitarget small molecules (MSM) for Alzheimer’s disease therapy. Contrary to our expectations, none of them showed significant human recombinant MAO inhibition, but compounds QN8, QN9, and DQN7 displayed promising human recombinant acetylcholinesterase (hrAChE) and butyrylcholinesterase (hrBuChE) inhibition. In particular, molecule QN8 was found to be a potent and quite selective non-competitive inhibitor of hrAChE (IC₅₀ = 0.29 µM), with K_i value in nanomolar range (79 nM). Pertinent docking analysis confirmed this result, suggesting that this ligand is an interesting hit for further investigation. Full article

(This article belongs to the Special Issue Acetylcholinesterase Inhibition in Neurogenesis, Neuroinflammation and Neurodegeneration Processes)

► Show Figures

Figure 1

Review

Jump to: Research

19 pages, 659 KiB

Open AccessReview

Allosterism of Nicotinic Acetylcholine Receptors: Therapeutic Potential for Neuroinflammation Underlying Brain Trauma and Degenerative Disorders

by Swarup Mitra, Shailesh N. Khatri, Malabika Maulik, Abel Bult-Ito and Marvin Schulte

Int. J. Mol. Sci. 2020, 21(14), 4918; https://doi.org/10.3390/ijms21144918 - 12 Jul 2020

Cited by 12 | Viewed by 5147

Abstract

Inflammation is a key physiological phenomenon that can be pervasive when dysregulated. Persistent chronic inflammation precedes several pathophysiological conditions forming one of the critical cellular homeostatic checkpoints. With a steady global surge in inflammatory diseases, it is imperative to delineate underlying mechanisms and design suitable drug molecules targeting the cellular partners that mediate and regulate inflammation. Nicotinic acetylcholine receptors have a confirmed role in influencing inflammatory pathways and have been a subject of scientific scrutiny underlying drug development in recent years. Drugs designed to target allosteric sites on the nicotinic acetylcholine receptors present a unique opportunity to unravel the role of the cholinergic system in regulating and restoring inflammatory homeostasis. Such a therapeutic approach holds promise in treating several inflammatory conditions and diseases with inflammation as an underlying pathology. Here, we briefly describe the potential of cholinergic allosterism and some allosteric modulators as a promising therapeutic option for the treatment of neuroinflammation. Full article

(This article belongs to the Special Issue Acetylcholinesterase Inhibition in Neurogenesis, Neuroinflammation and Neurodegeneration Processes)

► Show Figures

Figure 1

18 pages, 1108 KiB

Open AccessReview

Improving Anti-Neurodegenerative Benefits of Acetylcholinesterase Inhibitors in Alzheimer’s Disease: Are Irreversible Inhibitors the Future?

by Donald E. Moss

Int. J. Mol. Sci. 2020, 21(10), 3438; https://doi.org/10.3390/ijms21103438 - 13 May 2020

Cited by 54 | Viewed by 9776

Abstract

Decades of research have produced no effective method to prevent, delay the onset, or slow the progression of Alzheimer’s disease (AD). In contrast to these failures, acetylcholinesterase (AChE, EC 3.1.1.7) inhibitors slow the clinical progression of the disease and randomized, placebo-controlled trials in prodromal and mild to moderate AD patients have shown AChE inhibitor anti-neurodegenerative benefits in the cortex, hippocampus, and basal forebrain. CNS neurodegeneration and atrophy are now recognized as biomarkers of AD according to the National Institute on Aging-Alzheimer’s Association (NIA-AA) criteria and recent evidence shows that these markers are among the earliest signs of prodromal AD, before the appearance of amyloid. The current AChE inhibitors (donepezil, rivastigmine, and galantamine) have short-acting mechanisms of action that result in dose-limiting toxicity and inadequate efficacy. Irreversible AChE inhibitors, with a long-acting mechanism of action, are inherently CNS selective and can more than double CNS AChE inhibition possible with short-acting inhibitors. Irreversible AChE inhibitors open the door to high-level CNS AChE inhibition and improved anti-neurodegenerative benefits that may be an important part of future treatments to more effectively prevent, delay the onset, or slow the progression of AD. Full article

(This article belongs to the Special Issue Acetylcholinesterase Inhibition in Neurogenesis, Neuroinflammation and Neurodegeneration Processes)

► Show Figures