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Special Issue Editor

Dr. Feng-Shiun Shie

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Guest Editor

Center for Neuropsychiatric Research, National Health Research Institutes, No. 35 Keyan Road, Zhunan Town, Miaoli County 350, Taiwan
Interests: glial activation; glia-mediated neuro-inflammation; oxidative stress; insulin resistance; hyperlipidemia; Alzheimer's disease; immunotherapy; gene therapy; polyphenols; small molecule drugs; combination therapy; Chinese herbal medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Neurological disorders involve damage to the neuronal activity of the brain, spinal cord, or peripheral nervous system under multiple age and health conditions. Due to the complexity of the etiology and the clinical manifestation, an efficacious therapeutic regimen and a reliable diagnostic tool are still unmet medical needs.

Among the most prevalent neurological disorders, Alzheimer’s disease, epilepsy, multiple sclerosis, Parkinson’s disease, and stroke share many common pathological events, such as glial overactivation, neuronal dysfunction, and neuroinflammation. These neurological disorders cause neurodegeneration, which may lead to cognitive impairment. Many psychiatric diseases and pain also elicit neurological conditions with chronic neurodegeneration. Therefore, understanding the mechanisms underlying the pathogenesis of neurological disorders will confer a great opportunity to delineate therapeutic interventions. The innovative treatment paradigms include but not limited to small-molecule drugs, gene therapy, stem cell therapy, immunotherapy, and combination therapy. Importantly, the pathogenesis of many of these neurological disorders can occur long before the onset of clinical manifestations, and a diagnostic tool for early detection of the disease is a must.

This Special Issue invites submissions of original research articles, communications, and comprehensive reviews, encompassing advanced research on all neurological diseases. Articles that investigate novel molecular mechanisms from the perspective of diagnosis/therapy and focus on restoring glial/neuronal activity and/or diminishing neuroinflammation are especially welcome.

Dr. Feng-Shiun Shie
Guest Editor

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Keywords

neurological disorders
neurodegeneration
neuroinflammation
small-molecule drugs
gene therapy
stem cell therapy
immunotherapy
combination therapy
early diagnosis
pathogenesis

Published Papers (2 papers)

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Research

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21 pages, 17437 KiB

Open AccessArticle

Nucleobase-Derived Nitrones: Synthesis and Antioxidant and Neuroprotective Activities in an In Vitro Model of Ischemia–Reperfusion

by Beatriz Chamorro, Iwona E. Głowacka, Joanna Gotkowska, Rafał Gulej, Dimitra Hadjipavlou-Litina, Francisco López-Muñoz, José Marco-Contelles, Dorota G. Piotrowska and María Jesús Oset-Gasque

Int. J. Mol. Sci. 2022, 23(6), 3411; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23063411 - 21 Mar 2022

Cited by 2 | Viewed by 2296

Abstract

Herein, we report the synthesis, antioxidant, and neuroprotective properties of some nucleobase-derived nitrones named 9a–i. The neuroprotective properties of nitrones, 9a–i, were measured against an oxygen-glucose-deprivation in vitro ischemia model using human neuroblastoma SH-SY5Y cells. Our results indicate that nitrones, 9a–i, have better neuroprotective and antioxidant properties than α-phenyl-N-tert-butylnitrone (PBN) and are similar to N-acetyl-L-cysteine (NAC), a well-known antioxidant and neuroprotective agent. The nitrones with the highest neuroprotective capacity were those containing purine nucleobases (nitrones 9f, g, B = adenine, theophylline), followed by nitrones with pyrimidine nucleobases with H or F substituents at the C5 position (nitrones 9a, c). All of these possess EC₅₀ values in the range of 1–6 μM and maximal activities higher than 100%. However, the introduction of a methyl substituent (nitrone 9b, B = thymine) or hard halogen substituents such as Br and Cl (nitrones 9d, e, B = 5-Br and 5-Cl uracil, respectively) worsens the neuroprotective activity of the nitrone with uracil as the nucleobase (9a). The effects on overall metabolic cell capacity were confirmed by results on the high anti-necrotic (EC_50′s ≈ 2–4 μM) and antioxidant (EC_50′s ≈ 0.4–3.5 μM) activities of these compounds on superoxide radical production. In general, all tested nitrones were excellent inhibitors of superoxide radical production in cultured neuroblastoma cells, as well as potent hydroxyl radical scavengers that inhibit in vitro lipid peroxidation, particularly, 9c, f, g, presenting the highest lipoxygenase inhibitory activity among the tested nitrones. Finally, the introduction of two nitrone groups at 9a and 9d (bis-nitronas 9g, i) did not show better neuroprotective effects than their precursor mono-nitrones. These results led us to propose nitrones containing purine (9f, g) and pyrimidine (9a, c) nucleobases as potential therapeutic agents for the treatment of cerebral ischemia and/or neurodegenerative diseases, leading us to further investigate their effects using in vivo models of these pathologies. Full article

(This article belongs to the Special Issue Advanced Research on Neurological Disorders: From Novel Molecular Mechanism to Innovative Therapeutic Paradigm)

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Review

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32 pages, 1738 KiB

Open AccessReview

Epigenetic Modulation of Opioid Receptors by Drugs of Abuse

by Ke Zhang Reid, Brendan Matthew Lemezis, Tien-Chi Hou and Rong Chen

Int. J. Mol. Sci. 2022, 23(19), 11804; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231911804 - 05 Oct 2022

Cited by 3 | Viewed by 2616

Abstract

Chronic exposure to drugs of abuse produces profound changes in gene expression and neural activity associated with drug-seeking and taking behavior. Dysregulation of opioid receptor gene expression is commonly observed across a variety of abused substances including opioids, cocaine, and alcohol. Early studies in cultured cells showed that the spatial and temporal gene expression of opioid receptors are regulated by epigenetic mechanisms including DNA and histone modifications and non-coding RNAs. Accumulating evidence indicate that drugs of abuse can modulate opioid receptor gene expression by targeting various epigenetic regulatory networks. Based on current cellular and animal models of substance use disorder and clinical evidence, this review summarizes how chronic drug exposure alters the gene expression of mu, delta, kappa, and nociceptin receptors via DNA and histone modifications. The influence of drugs of abuse on epigenetic modulators, such as non-coding RNAs and transcription factors, is also presented. Finally, the therapeutic potential of manipulating epigenetic processes as an avenue to treat substance use disorder is discussed. Full article

(This article belongs to the Special Issue Advanced Research on Neurological Disorders: From Novel Molecular Mechanism to Innovative Therapeutic Paradigm)

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