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Metabolic Influences on Neurodegeneration

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

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 5430

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School of Psychology and Neuroscience, University of St Andrews, St Andrews KY16 9AJ, UK
Interests: neurology; neuroprotective actions of leptin; neuroprotective actions; leptin; deep-brain photoreception; neurodegeneration
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Special Issue Information

Dear Colleagues, 

Neurodegenerative diseases (NDDs) are characterized by a variety of cellular features, including neuronal loss, neuronal dysfunction in specific brain regions, aggregation of different proteins, impaired protein clearance, mitochondrial dysfunction, oxidative stress, neuroinflammation, axon transport defects, and cell death. For numerous cytopathologies, insufficient glucose metabolism and mitochondrial dysfunction are demonstrated to be early indicators of age-related functional changes during normal brain aging, such as in the case of Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). In addition to producing ATP, mitochondria are at the center of numerous metabolic pathways and important cellular functions, including fine-tuning of intracellular calcium (iCa2+) signaling, regulation of cell death, lipid synthesis, ROS signaling, and cell quality control. The signaling pathways that combine cellular energy metabolism with the adaptive structural and functional responses of neuronal circuits to neuronal network activity are quite complex. Future studies should aim to elucidate this intercellular and subcellular pathway. The aim of this Special Issue is to present novel evidence supporting the link between metabolism and neurodegeneration. Ultimately, the focus will be on how metabolic manipulations could be used as a therapeutic tool for neurodegenerative diseases.

Dr. Gayle Helane Doherty 
Guest Editor

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Published Papers (3 papers)

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Research

13 pages, 2553 KiB  
Article
Microwave-Assisted Synthesis of 3-Hydroxy-2-oxindoles and Pilot Evaluation of Their Antiglaucomic Activity
by Alexander M. Efremov, Olga V. Beznos, Roman O. Eremeev, Natalia B. Chesnokova, Elena R. Milaeva, Elena F. Shevtsova and Natalia A. Lozinskaya
Int. J. Mol. Sci. 2023, 24(6), 5101; https://doi.org/10.3390/ijms24065101 - 7 Mar 2023
Cited by 7 | Viewed by 1632
Abstract
Glaucoma is a widespread neurodegenerative disease for which increased intraocular pressure (IOP) is a primary modifiable risk factor. Recently, we have observed that compounds with oxindole scaffolds are involved in the regulation of intraocular pressure and therefore have potential antiglaucomic activity. In this [...] Read more.
Glaucoma is a widespread neurodegenerative disease for which increased intraocular pressure (IOP) is a primary modifiable risk factor. Recently, we have observed that compounds with oxindole scaffolds are involved in the regulation of intraocular pressure and therefore have potential antiglaucomic activity. In this article, we present an efficient method for obtaining novel 2-oxindole derivatives via microwave-assisted (MW) decarboxylative condensation of substituted isatins with malonic and cyanoacetic acids. Various 3-hydroxy-2-oxindoles were synthesized using MW activation for 5–10 min with high yields (up to 98%). The influence of novel compounds applied in instillations on IOP was studied in vivo on normotensive rabbits. The lead compound was found to reduce the IOP by 5.6 Torr (ΔIOP for the widely used antiglaucomatousic drug timolol 3.5 Torr and for melatonin 2.7 Torr). Full article
(This article belongs to the Special Issue Metabolic Influences on Neurodegeneration)
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18 pages, 2331 KiB  
Article
Blood Metabolomics May Discriminate a Sub-Group of Patients with First Demyelinating Episode in the Context of RRMS with Increased Disability and MRI Characteristics Indicative of Poor Prognosis
by Marina Boziki, Alexandros Pechlivanis, Christina Virgiliou, Christos Bakirtzis, Styliani Aggeliki Sintila, Eleni Karafoulidou, Evangelia Kesidou, Paschalis Theotokis, Ioannis Nikolaidis, Georgios Theodoridis, Helen Gika and Nikolaos Grigoriadis
Int. J. Mol. Sci. 2022, 23(23), 14578; https://doi.org/10.3390/ijms232314578 - 23 Nov 2022
Cited by 1 | Viewed by 1336
Abstract
Biomarker research across the health-to-disease continuum is being increasingly applied. We applied blood-based metabolomics in order to identify patient clusters with a first demyelinating episode, and explored the prognostic potential of the method by thoroughly characterizing each cluster in terms of clinical, laboratory [...] Read more.
Biomarker research across the health-to-disease continuum is being increasingly applied. We applied blood-based metabolomics in order to identify patient clusters with a first demyelinating episode, and explored the prognostic potential of the method by thoroughly characterizing each cluster in terms of clinical, laboratory and MRI markers of established prognostic potential for Multiple Sclerosis (MS). Recruitment consisted of 11 patients with Clinically Isolated Syndrome (CIS), 37 patients with a first demyelinating episode in the context of Relapsing-Remitting MS (RRMS) and 11 control participants. Blood-based metabolomics and hierarchical clustering analysis (HCL) were applied. Constructed OPLS-DA models illustrated a discrimination between patients with CIS and the controls (p = 0.0014), as well as between patients with RRMS and the controls (p = 1 × 10−5). Hierarchical clustering analysis (HCL) for patients with RRMS identified three clusters. RRMS-patients-cluster-3 exhibited higher mean cell numbers in the Cerebro-spinal Fluid (CSF) compared to patients with CIS (18.17 ± 6.3 vs. 1.09 ± 0.41, p = 0.004). Mean glucose CSF/serum ratio and infratentorial lesion burden significantly differed across CIS- and HCL-derived RRMS-patient clusters (F = 14.95, p < 0.001 and F = 6.087, p = 0.002, respectively), mainly due to increased mean values for patients with RRMS-cluster-3. HCL discriminated a cluster of patients with a first demyelinating episode in the context of RRMS with increased disability, laboratory findings linked with increased pathology burden and MRI markers of poor prognosis. Full article
(This article belongs to the Special Issue Metabolic Influences on Neurodegeneration)
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11 pages, 283 KiB  
Article
Analysis of ADORA2A rs5760423 and CYP1A2 rs762551 Genetic Variants in Patients with Alzheimer’s Disease
by Vasileios Siokas, Dimitra S. Mouliou, Ioannis Liampas, Athina-Maria Aloizou, Vasiliki Folia, Elli Zoupa, Anastasios Papadimitriou, Eleftherios Lavdas, Dimitrios P. Bogdanos and Efthimios Dardiotis
Int. J. Mol. Sci. 2022, 23(22), 14400; https://doi.org/10.3390/ijms232214400 - 19 Nov 2022
Cited by 6 | Viewed by 1940
Abstract
Various studies have been conducted, exploring the genetic susceptibility of Alzheimer’s disease (AD). Adenosine receptor subtype A2a (ADORA2A) and cytochrome P450 1A2 (CYP1A2) are implicated in pathways such as oxidative stress and caffeine metabolism, which are associated with AD. The aim of this [...] Read more.
Various studies have been conducted, exploring the genetic susceptibility of Alzheimer’s disease (AD). Adenosine receptor subtype A2a (ADORA2A) and cytochrome P450 1A2 (CYP1A2) are implicated in pathways such as oxidative stress and caffeine metabolism, which are associated with AD. The aim of this study was to explore for any potential association between the ADORA2A rs5760423 and the CYP1A2 rs762551 genetic variants and AD. A case–control study was performed with a total of 654 subjects (327 healthy controls and 327 patients with AD). Five genetic models were assumed. We also examined the allele–allele combination of both variants. The value of 0.05 was considered as the statistical significance threshold. A statistically significant association was found between ADORA2A rs5760423 and AD, as the “T” allele was associated with increased AD risk in recessive (OR = 1.51 (1.03–2.21)) and log-additive (OR = 1.30 (1.04–1.62)) genetic modes. In the codominant model, the TT genotype was more prevalent compared to the GG genotype (OR = 1.71 (1.09–2.66)). The statistical significance was maintained after adjustment for sex. No association between CYP1A2 rs762551 or allele–allele combination and AD was detected. We provide preliminary indication for a possible association between the ADORA2A rs5760423 genetic polymorphism and AD. Full article
(This article belongs to the Special Issue Metabolic Influences on Neurodegeneration)
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