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Discovering New Drug Targets for Neurodegenerative Disorders

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

Deadline for manuscript submissions: closed (30 November 2024) | Viewed by 4913

Special Issue Editors


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Guest Editor
1. Department of Molecular Biology and Genetics, Burdur Mehmet Akif Ersoy University, Burdur 15030, Türkiye
2. Department of Bioengineering Sciences, Izmir Katip Celebi University, Izmir 35620, Türkiye
3. Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto 862-0976, Japan
4. Department of Drug Discovery, Science Farm Ltd., Kumamoto 862-0976, Japan
Interests: structure-based drug discovery; molecular simulations; drug repositioning; structural biology; molecular modelling; QSAR; virtual screening
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Guest Editor
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskisehir, Turkey
Interests: medicinal chemistry; computational chemistry; QSAR; molecular modelling; molecular simulations; virtual screening; in silico ADME analysis; drug design and development
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Chemical Physics of Nanomaterials, Baku State University, Baku, Azerbaijan
Interests: nanotechnology; nanochemistry; probe microscopy; ion-track nanotechnology; synthesis and stabilization of nanoparticles; polymer nanocomposites; magnetic nanocomposites for adsorption of high frequency electromagnetic waves; electret nanocomposites for sensor techniques; application of nanomaterials in ecology; removal of nitrates using bimetallic nanoparticles; magnetic nanoparticles for dye degradation and other

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Guest Editor
1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey
2. Dean of Faculty of Pharmacy, İzmir Katip Çelebi University, İzmir, Turkey
Interests: medicinal chemistry; organic chemistry; kojic acid derivatives; Mannich bases in drug design; hydroxypyranones/hydroxypyridinones in neurodegenerative diseases

Special Issue Information

Dear Colleagues,

Neurodegenerative disorders share familiar pathological features, including the selective deterioration and progressive loss of synapses and neurons as well as the accumulation of certain proteins into insoluble aggregates in damaged neurons and glial cells. However, these disorders, such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS), display great diversity in their clinical phenotypes. Despite the advancements in the treatments of these disorders, there is no effective disease-modifying therapy available so far. Current treatment options are only beneficial in the temporary improvement of symptoms. In particular, the multifaceted nature of these disorders, affected by many pathological mechanisms, is one of the major obstacles that needs to be defeated to find an effective cure.

This Special Issue aims to provide deep mechanistic insights into new treatment strategies in targeted drug development against neurodegenerative disorders. It is our great pleasure to invite you to submit original research articles and reviews associated with the identification of natural and synthetic compounds that are effective against neurodegenerative disorders and that act on relevant signaling pathways and downstream molecular targets involved in the deregulation of neurogenesis.

Research areas may include (but are not limited to) the following:

  • Oxidative mechanisms in neurodegenerative disorders;
  • Therapeutic targets for Alzheimer’s disease;
  • Therapeutic targets for Parkinson’s disease;
  • Therapeutic targets for amyotrophic lateral sclerosis (ALS);
  • In silico approaches against neurodegenerative disorders;
  • The importance of the blood–brain barrier (BBB) in neurodegenerative disorders;
  • In vitro and in vivo activity studies against neurodegenerative disorders;
  • Nanoparticles and their use in neurodegenerative disorders;
  • Determination of the pharmacokinetic parameters of compounds that are effective against neurodegenerative disorders;
  • Current treatment strategies for neurodegenerative disorders;
  • Synthesis and evaluation of new compounds against neurodegenerative disorders.

Dr. Halil İbrahim Ciftci
Dr. Belgin Sever
Dr. Flora Vidadi Hajiyeva
Prof. Dr. Mutlu Aytemir
Guest Editors

Manuscript Submission Information

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Keywords

  • neurodegenerative disorders
  • Alzheimer’s disease
  • Parkinson’s disease
  • amyotrophic lateral sclerosis (ALS)
  • specific enzyme regulation in neurodegenerative disorders
  • in silico approaches against neurodegenerative disorders
  • drug discovery in neurodegenerative disorders
  • determination of pharmacokinetic parameters in neurodegenerative disorders
  • targeted therapy for neurodegenerative disorders
  • current treatment strategies for neurodegenerative disorders

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Published Papers (2 papers)

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Research

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11 pages, 2508 KiB  
Article
Osthole Antagonizes Microglial Activation in an NRF2-Dependent Manner
by Chuan-Hsiu Liu, Mei-Ying Chen, Yueh-Hsiung Kuo, Jack Cheng, Li-Zhong Chang, Meng-Shiun Chang, Tsai-Ni Chuang, Wen-Tsong Hsieh, Yan-Ru Xiao, Bor-Tsang Wu, Wei-Yong Lin and Hsin-Ping Liu
Molecules 2023, 28(2), 507; https://doi.org/10.3390/molecules28020507 - 4 Jan 2023
Cited by 4 | Viewed by 1974
Abstract
Microglia are neuroglia in the brain with an innate immune function and participate in the progress of neurodegenerative diseases. Osthole (OST) is a coumarin derivative extracted from Cnidium monnieri and bears a microglia-antagonizing ability. However, the underlying mechanism of the antagonism is not [...] Read more.
Microglia are neuroglia in the brain with an innate immune function and participate in the progress of neurodegenerative diseases. Osthole (OST) is a coumarin derivative extracted from Cnidium monnieri and bears a microglia-antagonizing ability. However, the underlying mechanism of the antagonism is not clear. The lipopolysaccharides-induced microglial BV2 cell line and amyloid-overexpressing fruit fly were used as models to study OST treatment. We found that OST treatment is sufficient to evoke NRF2 cascade under an LPS-induced inflammatory environment, and silencing NRF2 is sufficient to abolish the process. Moreover, we found that OST is sufficient to antagonize microglial activation in both LPS-induced BV2 cells and Aβ-overexpressing fruit flies, and silencing NRF2 abolishes OST’s antagonism. Furthermore, OST treatment rescued survival, climbing, and the learning ability of Aβ-overexpressing fruit flies and relieved oxidative stress. In conclusion, we proved that OST antagonizes microglial activation induced by either LPS or Aβ and that NRF2 is necessary for OST’s antagonism. Full article
(This article belongs to the Special Issue Discovering New Drug Targets for Neurodegenerative Disorders)
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Review

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27 pages, 4630 KiB  
Review
Glutamate: Molecular Mechanisms and Signaling Pathway in Alzheimer’s Disease, a Potential Therapeutic Target
by Nidhi Puranik and Minseok Song
Molecules 2024, 29(23), 5744; https://doi.org/10.3390/molecules29235744 - 5 Dec 2024
Viewed by 1256
Abstract
Gamma-glutamate is an important excitatory neurotransmitter in the central nervous system (CNS), which plays an important role in transmitting synapses, plasticity, and other brain activities. Nevertheless, alterations in the glutamatergic signaling pathway are now accepted as a central element in Alzheimer’s disease (AD) [...] Read more.
Gamma-glutamate is an important excitatory neurotransmitter in the central nervous system (CNS), which plays an important role in transmitting synapses, plasticity, and other brain activities. Nevertheless, alterations in the glutamatergic signaling pathway are now accepted as a central element in Alzheimer’s disease (AD) pathophysiology. One of the most prevalent types of dementia in older adults is AD, a progressive neurodegenerative illness brought on by a persistent decline in cognitive function. Since AD has been shown to be multifactorial, a variety of pharmaceutical targets may be used to treat the condition. N-methyl-D-aspartic acid receptor (NMDAR) antagonists and acetylcholinesterase inhibitors (AChEIs) are two drug classes that the Food and Drug Administration has authorized for the treatment of AD. The AChEIs approved to treat AD are galantamine, donepezil, and rivastigmine. However, memantine is the only non-competitive NMDAR antagonist that has been authorized for the treatment of AD. This review aims to outline the involvement of glutamate (GLU) at the molecular level and the signaling pathways that are associated with AD to demonstrate the drug target therapeutic potential of glutamate and its receptor. We will also consider the opinion of the leading authorities working in this area, the drawback of the existing therapeutic strategies, and the direction for the further investigation. Full article
(This article belongs to the Special Issue Discovering New Drug Targets for Neurodegenerative Disorders)
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