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Special Issue "Development of Novel Drugs for Alzheimer's Disease and Myasthenia Gravis"

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

Deadline for manuscript submissions: closed (21 July 2019).

Special Issue Editors

Guest Editor
Prof. Dr. Kamil Kuca

University of Hradec Kralove, Hradec Kralove, Czech Republic
Website | E-Mail
Phone: +420603289166
Interests: Antidotes for pesticide and nerve agent poisonings; Alzheimer’s disease treatment; Detergents as disinfectants, nanoparticles; decontamination means; Toxins; Drug design and development; Nanotechnology; IT, parallel computing, ANN; Project management; Scientific management; Technology Transfer; Health economics and Pharmacoeconomics
Guest Editor
Assoc. Prof. Martin Valis

Neurology Clinic, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic
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Guest Editor
Dr. Eugenie Nepovimova

Faculty of Science, University of Hradec Kralove, Czech Republic,
Website | E-Mail

Special Issue Information

Dear Colleagues,

Searching for novel drugs for the treatment of Alzheimer’s disease (AD) became a main task of current developed societies. There were/are and will be novel drug candidates designed, synthesized and tested throughout many places of the world. Despite tremendous advances in understanding many aspects of AD pathogenesis, there are no proven disease-modifying therapies and the only available ones are minimally effective symptomatic therapies.

Myasthenia gravis (MG) is a neuromuscular disorder that causes weakness in the skeletal muscles. Myasthenia gravis is caused by a breakdown in the normal communication between nerves and muscles. In the case of this disease, efficacy of currently-available drugs is limited.

Both diseases (AD and MG) are associated with an enzyme acetylcholinesterase (AChE), which is a target for development on novel drug candidates for these diseases.

In this Special Issue of International Journal of Molecular Sciences, we would like to discuss all chemico-biological aspects, which are behind the Alzheimer’s disease, as well as Myasthenia gravis.

Prof. Dr. Kamil Kuca
Assoc. Prof. Martin Valis
Dr. Eugenie Nepovimova
Guest Editors

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 papers will be 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

  • Alzheimer’s Disease
  • Treatment
  • Drug Development
  • Computational Chemistry
  • Molecular Biology
  • Diagnosis
  • In Vitro & In Vivo
  • Biochemistry

Published Papers (5 papers)

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Research

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Open AccessArticle
Synthesis of New Quinoline-Piperonal Hybrids as Potential Drugs against Alzheimer’s Disease
Int. J. Mol. Sci. 2019, 20(16), 3944; https://doi.org/10.3390/ijms20163944
Received: 2 June 2019 / Revised: 1 August 2019 / Accepted: 9 August 2019 / Published: 14 August 2019
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Abstract
Six quinoline-piperonal hybrids were synthesized and evaluated as potential drugs against Alzheimer’s disease (AD). Theoretical analysis of the pharmacokinetic and toxicological properties of the compounds suggest that they present good oral bio-availability and are also capable of penetrating the blood–brain barrier, qualifying as [...] Read more.
Six quinoline-piperonal hybrids were synthesized and evaluated as potential drugs against Alzheimer’s disease (AD). Theoretical analysis of the pharmacokinetic and toxicological properties of the compounds suggest that they present good oral bio-availability and are also capable of penetrating the blood–brain barrier, qualifying as leads for new drugs against AD. Evaluation of their inhibitory capacity against acetyl- and butyrilcholinesterases (AChE and BChE) through Ellmann’s test showed that three compounds present promising results with one of them being capable of inhibiting both enzymes. Further docking studies of the six compounds synthesized helped to elucidate the main interactions that may be responsible for the inhibitory activities observed. Full article
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Review

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Open AccessReview
Neuropharmacology of the Neuropsychiatric Symptoms of Dementia and Role of Pain: Essential Oil of Bergamot as a Novel Therapeutic Approach
Int. J. Mol. Sci. 2019, 20(13), 3327; https://doi.org/10.3390/ijms20133327
Received: 10 June 2019 / Revised: 24 June 2019 / Accepted: 5 July 2019 / Published: 6 July 2019
PDF Full-text (734 KB) | HTML Full-text | XML Full-text
Abstract
Aging of the population makes of dementia a challenge for health systems worldwide. The cognitive disturbance is a serious but not the only issue in dementia; behavioral and psychological syndromes known as neuropsychiatric symptoms of dementia remarkably reduce the quality of life. The [...] Read more.
Aging of the population makes of dementia a challenge for health systems worldwide. The cognitive disturbance is a serious but not the only issue in dementia; behavioral and psychological syndromes known as neuropsychiatric symptoms of dementia remarkably reduce the quality of life. The cluster of symptoms includes anxiety, depression, wandering, delusions, hallucinations, misidentifications, agitation and aggression. The pathophysiology of these symptoms implicates all the neurotransmitter systems, with a pivotal role for the glutamatergic neurotransmission. Imbalanced glutamatergic and GABAergic neurotransmissions, over-activation of the extrasynaptic N-methyl-D-aspartate (NMDA) receptors and alterations of the latter have been linked to the development of neuropsychiatric symptoms experienced by almost the entire demented population. Drugs with efficacy and safety for prevention or long term treatment of these disorders are not available yet. Aromatherapy provides the best evidence for positive outcomes in the control of agitation, the most resistant symptom. Demented patients often cannot verbalize pain, resulting in unrelieved symptoms and contributing to agitation. Bergamot essential oil provides extensive preclinical evidence of analgesic properties. Incidentally, the essential oil of bergamot induces anxyolitic-like effects devoid of sedation, typical of benzodiazepines, with a noteworthy advantage for demented patients. These data, together with the reported safety profile, form the rational basis for bergamot as a neurotherapeutic to be trialed for the control of behavioral and psychological symptoms of dementia. Full article
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Open AccessReview
Approaches to CNS Drug Delivery with a Focus on Transporter-Mediated Transcytosis
Int. J. Mol. Sci. 2019, 20(12), 3108; https://doi.org/10.3390/ijms20123108
Received: 27 May 2019 / Revised: 15 June 2019 / Accepted: 16 June 2019 / Published: 25 June 2019
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Abstract
Drug delivery to the central nervous system (CNS) conferred by brain barriers is a major obstacle in the development of effective neurotherapeutics. In this review, a classification of current approaches of clinical or investigational importance for the delivery of therapeutics to the CNS [...] Read more.
Drug delivery to the central nervous system (CNS) conferred by brain barriers is a major obstacle in the development of effective neurotherapeutics. In this review, a classification of current approaches of clinical or investigational importance for the delivery of therapeutics to the CNS is presented. This classification includes the use of formulations administered systemically that can elicit transcytosis-mediated transport by interacting with transporters expressed by transvascular endothelial cells. Neurotherapeutics can also be delivered to the CNS by means of surgical intervention using specialized catheters or implantable reservoirs. Strategies for delivering drugs to the CNS have evolved tremendously during the last two decades, yet, some factors can affect the quality of data generated in preclinical investigation, which can hamper the extension of the applications of these strategies into clinically useful tools. Here, we disclose some of these factors and propose some solutions that may prove valuable at bridging the gap between preclinical findings and clinical trials. Full article
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Open AccessReview
Recent Developments in Metal-Based Drugs and Chelating Agents for Neurodegenerative Diseases Treatments
Int. J. Mol. Sci. 2019, 20(8), 1829; https://doi.org/10.3390/ijms20081829
Received: 17 February 2019 / Revised: 7 April 2019 / Accepted: 9 April 2019 / Published: 12 April 2019
Cited by 1 | PDF Full-text (3817 KB) | HTML Full-text | XML Full-text
Abstract
The brain has a unique biological complexity and is responsible for important functions in the human body, such as the command of cognitive and motor functions. Disruptive disorders that affect this organ, e.g., neurodegenerative diseases (NDDs), can lead to permanent damage, impairing the [...] Read more.
The brain has a unique biological complexity and is responsible for important functions in the human body, such as the command of cognitive and motor functions. Disruptive disorders that affect this organ, e.g., neurodegenerative diseases (NDDs), can lead to permanent damage, impairing the patients’ quality of life and even causing death. In spite of their clinical diversity, these NDDs share common characteristics, such as the accumulation of specific proteins in the cells, the compromise of the metal ion homeostasis in the brain, among others. Despite considerable advances in understanding the mechanisms of these diseases and advances in the development of treatments, these disorders remain uncured. Considering the diversity of mechanisms that act in NDDs, a wide range of compounds have been developed to act by different means. Thus, promising compounds with contrasting properties, such as chelating agents and metal-based drugs have been proposed to act on different molecular targets as well as to contribute to the same goal, which is the treatment of NDDs. This review seeks to discuss the different roles and recent developments of metal-based drugs, such as metal complexes and metal chelating agents as a proposal for the treatment of NDDs. Full article
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Open AccessReview
Drug Development for Alzheimer’s Disease: Microglia Induced Neuroinflammation as a Target?
Int. J. Mol. Sci. 2019, 20(3), 558; https://doi.org/10.3390/ijms20030558
Received: 27 December 2018 / Revised: 9 January 2019 / Accepted: 13 January 2019 / Published: 28 January 2019
Cited by 2 | PDF Full-text (699 KB) | HTML Full-text | XML Full-text
Abstract
Alzheimer’s disease (AD) is one of the most common causes of dementia. Its pathogenesis is characterized by the aggregation of the amyloid-β (Aβ) protein in senile plaques and the hyperphosphorylated tau protein in neurofibrillary tangles in the brain. Current medications for AD can [...] Read more.
Alzheimer’s disease (AD) is one of the most common causes of dementia. Its pathogenesis is characterized by the aggregation of the amyloid-β (Aβ) protein in senile plaques and the hyperphosphorylated tau protein in neurofibrillary tangles in the brain. Current medications for AD can provide temporary help with the memory symptoms and other cognitive changes of patients, however, they are not able to stop or reverse the progression of AD. New medication discovery and the development of a cure for AD is urgently in need. In this review, we summarized drugs for AD treatments and their recent updates, and discussed the potential of microglia induced neuroinflammation as a target for anti-AD drug development. Full article
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Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
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