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Neuroprotective Agents to Treat Dementias

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (31 December 2019) | Viewed by 17582

Special Issue Editor


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Guest Editor
Department of Pharmacy, University of Pisa, Via Bonanno, 6, 56126 Pisa, Italy
Interests: drug discovery; synthesis and structure–activity relationships of biologically active compounds; multitarget agents; hybrid compounds; kinase inhibitors; pro-autophagic molecules; neuroprotective agents; antioxidant molecules; medicinal chemistry
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Special Issue Information

Dear Colleagues,

Alzheimer’s disease (AD) is a progressive age-dependent and multi-factorial neurodegenerative pathology that leads to cognitive dysfunction and continues to have a significant impact on society as a whole. Given that the main drawback of AD therapy remains to be its limited effectiveness, the search for new potential drugs is heavily pursued. Several pathways are involved in AD’s etio-pathology, both in peripheral and central human districts that include aberrant lipid metabolism, oxidative stress, mitochondrial impairment, neuroinflammatory processes, impairment of autophagic flux, and blood–brain barrier (BBB) disruption.

This Special Issue “Neuroprotective Agents to Treat Dementias” welcomes the submission of review and research articles related to the design and synthesis of new molecules that could provide an innovative approach for the treatment of AD or other forms of dementia, including mechanisms and pharmacological characterization. Moreover, full research articles and/or reviews covering drugs repurposing approaches in neurodegenerative diseases are welcome.

Prof. Dr. Simona Rapposelli
Guest Editor

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). 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

  • autophagy inducers
  • antioxidant agents
  • neuroinflammation
  • dementia
  • anti-ageing agents
  • multitarget drugs
  • GSK3
  • metabolic disorders
  • sirtuin
  • NrF2-ARE pathway
  • oxidative stress
  • mitochondrial dysfunction
  • metal chelating agents
  • Alzheimer’s disease
  • Repurposing drugs

Published Papers (3 papers)

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Research

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15 pages, 3161 KiB  
Article
Preparation of Benzothiazolyl-Decorated Nanoliposomes
by Spyridon Mourtas, Panayiota Christodoulou, Pavlos Klepetsanis, Dimitrios Gatos, Kleomenis Barlos and Sophia G. Antimisiaris
Molecules 2019, 24(8), 1540; https://doi.org/10.3390/molecules24081540 - 18 Apr 2019
Cited by 9 | Viewed by 3231
Abstract
Amyloid β (Aβ) species are considered as potential targets for the development of diagnostics/therapeutics towards Alzheimer’s disease (AD). Nanoliposomes which are decorated with molecules having high affinity for Aβ species may be considered as potential carriers for AD theragnostics. Herein, benzothiazolyl (BTH) decorated [...] Read more.
Amyloid β (Aβ) species are considered as potential targets for the development of diagnostics/therapeutics towards Alzheimer’s disease (AD). Nanoliposomes which are decorated with molecules having high affinity for Aβ species may be considered as potential carriers for AD theragnostics. Herein, benzothiazolyl (BTH) decorated nanoliposomes were prepared for the first time, after synthesis of a lipidic BTH derivative (lipid-BTH). The synthetic pathway included acylation of bis(2-aminophenyl) disulfide with palmitic acid or palmitoyl chloride and subsequent reduction of the oxidized dithiol derivative. The liberated thiols were able to cyclize to the corresponding benzothiazolyl derivatives only after acidification of the reaction mixture. Each step of the procedure was monitored by HPLC analysis in order to identify all the important parameters for the formation of the BTH-group. Finally, the optimal methodology was identified, and was applied for the synthesis of the lipid-BTH derivative. BTH-decorated nanoliposomes were then prepared and characterized for physicochemical properties (size distribution, surface charge, physical stability, and membrane integrity during incubation in presence of buffer and plasma proteins). Pegylated BTH-nanoliposomes were demonstrated to have high integrity in the presence of proteins (in comparison to non-peglated ones) justifying their further exploitation as potential theragnostic systems for AD. Full article
(This article belongs to the Special Issue Neuroprotective Agents to Treat Dementias)
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Review

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27 pages, 2298 KiB  
Review
Are Kynurenines Accomplices or Principal Villains in Dementia? Maintenance of Kynurenine Metabolism
by Masaru Tanaka, Zsuzsanna Bohár and László Vécsei
Molecules 2020, 25(3), 564; https://doi.org/10.3390/molecules25030564 - 28 Jan 2020
Cited by 69 | Viewed by 9184
Abstract
Worldwide, 50 million people suffer from dementia, a group of symptoms affecting cognitive and social functions, progressing severely enough to interfere with daily life. Alzheimer’s disease (AD) accounts for most of the dementia cases. Pathological and clinical findings have led to proposing several [...] Read more.
Worldwide, 50 million people suffer from dementia, a group of symptoms affecting cognitive and social functions, progressing severely enough to interfere with daily life. Alzheimer’s disease (AD) accounts for most of the dementia cases. Pathological and clinical findings have led to proposing several hypotheses of AD pathogenesis, finding a presence of positive feedback loops and additionally observing the disturbance of a branch of tryptophan metabolism, the kynurenine (KYN) pathway. Either causative or resultant of dementia, elevated levels of neurotoxic KYN metabolites are observed, potentially upregulating multiple feedback loops of AD pathogenesis. Memantine is an N-methyl-D-aspartate glutamatergic receptor (NMDAR) antagonist, which belongs to one of only two classes of medications approved for clinical use, but other NMDAR modulators have been explored so far in vain. An endogenous KYN pathway metabolite, kynurenic acid (KYNA), likewise inhibits the excitotoxic NMDAR. Besides its anti-excitotoxicity, KYNA is a multitarget compound that triggers anti-inflammatory and antioxidant activities. Modifying the KYNA level is a potential multitarget strategy to normalize the disturbed KYN pathway and thus to alleviate juxtaposing AD pathogeneses. In this review, the maintenance of KYN metabolism by modifying the level of KYNA is proposed and discussed in search for a novel lead compound against the progression of dementia. Full article
(This article belongs to the Special Issue Neuroprotective Agents to Treat Dementias)
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14 pages, 1414 KiB  
Review
White Matter and Neuroprotection in Alzheimer’s Dementia
by Luca Lorenzini, Mercedes Fernandez, Vito Antonio Baldassarro, Andrea Bighinati, Alessandro Giuliani, Laura Calzà and Luciana Giardino
Molecules 2020, 25(3), 503; https://doi.org/10.3390/molecules25030503 - 23 Jan 2020
Cited by 17 | Viewed by 4307
Abstract
Myelin is the main component of the white matter of the central nervous system (CNS), allowing the proper electrical function of the neurons by ensheathing and insulating the axons. The extensive use of magnetic resonance imaging has highlighted the white matter alterations in [...] Read more.
Myelin is the main component of the white matter of the central nervous system (CNS), allowing the proper electrical function of the neurons by ensheathing and insulating the axons. The extensive use of magnetic resonance imaging has highlighted the white matter alterations in Alzheimer’s dementia (AD) and other neurodegenerative diseases, alterations which are early, extended, and regionally selective. Given that the white matter turnover is considerable in the adulthood, and that myelin repair is currently recognized as being the only true reparative capability of the mature CNS, oligodendrocyte precursor cells (OPCs), the cells that differentiate in oligodendrocyte, responsible for myelin formation and repair, are regarded as a potential target for neuroprotection. In this review, several aspects of the OPC biology are reviewed. The histology and functional role of OPCs in the neurovascular-neuroglial unit as described in preclinical and clinical studies on AD is discussed, such as the OPC vulnerability to hypoxia-ischemia, neuroinflammation, and amyloid deposition. Finally, the position of OPCs in drug discovery strategies for dementia is discussed. Full article
(This article belongs to the Special Issue Neuroprotective Agents to Treat Dementias)
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