Channel Modulation in Neurodegeneration and Neuroprotection

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 4772

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School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong
Interests: Chinese medicine; pancreatic cancer; prostate cancer; herb-drug interaction; resistance
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Special Issue Information

Dear Colleagues,

 Ion channels are widely expressed in the central and peripheral nervous system and are crucial mediators of neuronal excitability. They play an important role in neurological and neurodegenerative conditions such as epilepsy, Parkinson’s, Huntington’s, and Alzheimer’s disease.  This Special Issue will provide a multidisciplinary platform for discussing pharmacological studies on ion channels and the implication thereof in neurodegeneration. This issue accepts original high-quality research articles that are not yet published or sought for publication. Please feel free to discuss your planned submission with the editor. Potential topics include but are not limited to the following: 

  • Therapeutic mechanism of neurodegeneration and neurodegenerative diseases;·       
  • Design and development of novel modulators of channels that may find application in neurological disorders.

Dr. Yan-Fang Xian
Guest Editor

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Published Papers (2 papers)

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Research

13 pages, 2329 KiB  
Article
In Silico and In Vitro Screening of Serine Racemase Agonist and In Vivo Efficacy on Alzheimer’s Disease Drosophila melanogaster
by Chih-Hao Lu, Hao-Teng Chang, Lee-Fen Hsu, Ming-Hsueh Lee, Jack Cheng, Dong Chuan Wu and Wei-Yong Lin
Pharmaceuticals 2023, 16(2), 280; https://doi.org/10.3390/ph16020280 - 13 Feb 2023
Cited by 1 | Viewed by 1824
Abstract
The NMDA receptor hypofunction has been implicated in schizophrenia, memory impairment, and Alzheimer’s disease. Modulating the abundance of D-serine, a co-agonist of the NMDA receptor, is a strategy to treat symptoms of the NMDA receptor hypofunction. In contrast to D-amino acid oxidase (DAAO) [...] Read more.
The NMDA receptor hypofunction has been implicated in schizophrenia, memory impairment, and Alzheimer’s disease. Modulating the abundance of D-serine, a co-agonist of the NMDA receptor, is a strategy to treat symptoms of the NMDA receptor hypofunction. In contrast to D-amino acid oxidase (DAAO) inhibitors, which aim at decreasing the loss of D-serine, this study tried to identify serine racemase (SRR) agonists, which boost the conversion of L-serine to D-serine. We used holo and apo structures of human SRR for the molecular docking against the National Cancer Institute (NCI) and ZINC compound databases and validated their efficacy by in vitro SRR activity assay. We identified NSC294149 (2-amino-3-(3-nitroimidazo[1,2-a]pyridin-2-yl)sulfanylpropanoic acid) as a potential SRR agonist and confirmed its amelioration of the hazard ratio of survival of the AD model of fruit fly (Drosophila melanogaster). These results suggest that the SRR agonist could be a drug design target against the NMDA receptor hypofunction symptoms. Full article
(This article belongs to the Special Issue Channel Modulation in Neurodegeneration and Neuroprotection)
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14 pages, 2827 KiB  
Article
Antiseizure Effects of Cannabidiol Leading to Increased Peroxisome Proliferator-Activated Receptor Gamma Levels in the Hippocampal CA3 Subfield of Epileptic Rats
by Anna-Maria Costa, Fabiana Russo, Lara Senn, Davide Ibatici, Giuseppe Cannazza and Giuseppe Biagini
Pharmaceuticals 2022, 15(5), 495; https://doi.org/10.3390/ph15050495 - 19 Apr 2022
Cited by 14 | Viewed by 2542
Abstract
We evaluated the effects of cannabidiol (CBD) on seizures and peroxisome proliferator-activated receptor gamma (PPARγ) levels in an animal model of temporal lobe epilepsy (TLE). Adult male Sprague-Dawley rats were continuously monitored by video-electrocorticography up to 10 weeks after an intraperitoneal kainic acid [...] Read more.
We evaluated the effects of cannabidiol (CBD) on seizures and peroxisome proliferator-activated receptor gamma (PPARγ) levels in an animal model of temporal lobe epilepsy (TLE). Adult male Sprague-Dawley rats were continuously monitored by video-electrocorticography up to 10 weeks after an intraperitoneal kainic acid (15 mg/kg) injection. Sixty-seven days after the induction of status epilepticus and the appearance of spontaneous recurrent seizures in all rats, CBD was dissolved in medium-chain triglyceride (MCT) oil and administered subcutaneously at 120 mg/kg (n = 10) or 12 mg/kg (n = 10), twice a day for three days. Similarly, the vehicle was administered to ten epileptic rats. Brain levels of PPARγ immunoreactivity were compared to those of six healthy controls. CBD at 120 mg/kg abolished the seizures in 50% of rats (p = 0.033 vs. pre-treatment, Fisher’s exact test) and reduced total seizure duration (p < 0.05, Tukey Test) and occurrence (p < 0.05). PPARγ levels increased with CBD in the hippocampal CA1 subfield and subiculum (p < 0.05 vs. controls, Holm–Šidák test), but only the highest dose increased the immunoreactivity in the hippocampal CA3 subfield (p < 0.001), perirhinal cortex, and amygdala (p < 0.05). Overall, these results suggest that the antiseizure effects of CBD are associated with upregulation of PPARγ in the hippocampal CA3 region. Full article
(This article belongs to the Special Issue Channel Modulation in Neurodegeneration and Neuroprotection)
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