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Lipids in Neurodegenerative Disorders
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Lipids in Neurodegenerative Disorders

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 October 2022) | Viewed by 8066

Special Issue Editors

Prof. Dr. Giuseppe Astarita

E-Mail Website
Guest Editor
Department of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington, DC 20007, USA
Interests: lipidomics; metabolomics; neurodegeneration; metabolic disorders; nutrition
Dr. Cristina Legido-Quigley

E-Mail Website
Guest Editor
Steno Diabetes Center, 2820 Gentofte, Denmark
Interests: lipidomics; metabolomics; brain-liver axis; dementia; diabetes; metabolism

Special Issue Information

Dear Colleagues,

In recent decades, there has been an increasing understanding of the various roles played by lipids in the central and peripheral nervous systems, mediating key biological processes from neuroinflammation to neurotransmission. Thus, dysfunction in lipid metabolism, either in the brain or periphery, is implicated in the pathophysiology of various neurodegenerative disorders, including Alzheimer’s disease, Parkinson's disease, and multiple sclerosis. Lipid pathways are becoming an attractive target for therapeutic interventions aiming to treat neurodegeneration, and lipids are often used as biomarkers in the drug development process.

This Special Issue will collect original research articles and review papers describing and elucidating any aspect of lipid metabolism that promotes or accompanies neurodegeneration.

Prof. Dr. Giuseppe Astarita
Dr. Cristina Legido-Quigley
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • lipid metabolism
  • lipidomics
  • neurodegeneration
  • dementia
  • Alzheimer’s
  • Parkinson
  • multiple sclerosis
  • neuroinflammation
  • liver–brain axis
  • gut–brain axis

Published Papers (3 papers)

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Research

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14 pages, 1405 KiB  
Article
Correlations between the NMR Lipoprotein Profile, APOE Genotype, and Cholesterol Efflux Capacity of Fasting Plasma from Cognitively Healthy Elderly Adults
by Itziar de Rojas, Laura del Barrio, Isabel Hernández, Laura Montrreal, Pablo García-González, Marta Marquié, Sergi Valero, Amanda Cano, Adelina Orellana, Mercè Boada, Santos Mañes and Agustín Ruiz
Int. J. Mol. Sci. 2023, 24(3), 2186; https://doi.org/10.3390/ijms24032186 - 22 Jan 2023
Cited by 2 | Viewed by 1644
Abstract
Cholesterol efflux capacity (CEC) is of interest given its potential relationship with several important clinical conditions including Alzheimer’s disease. The inactivation of the APOE locus in mouse models supports the idea that it is involved in determining the CEC. With that in mind, [...] Read more.
Cholesterol efflux capacity (CEC) is of interest given its potential relationship with several important clinical conditions including Alzheimer’s disease. The inactivation of the APOE locus in mouse models supports the idea that it is involved in determining the CEC. With that in mind, we examine the impact of the plasma metabolome profile and the APOE genotype on the CEC in cognitively healthy elderly subjects. The study subjects were 144 unrelated healthy individuals. The plasma CEC was determined by exposing cultured mouse macrophages treated with BODIPY-cholesterol to human plasma. The metabolome profile was determined using NMR techniques. Multiple regression was performed to identify the most important predictors of CEC, as well as the NMR features most strongly associated with the APOE genotype. Plasma 3-hydroxybutyrate was the variable most strongly correlated with the CEC (r = 0.365; p = 7.3 × 10−6). Male sex was associated with a stronger CEC (r = −0.326, p = 6.8 × 10−5). Most of the NMR particles associated with the CEC did not correlate with the APOE genotype. The NMR metabolomics results confirmed the APOE genotype to have a huge effect on the concentration of plasma lipoprotein particles as well as those of other molecules including omega-3 fatty acids. In conclusion, the CEC of human plasma was associated with ketone body concentration, sex, and (to a lesser extent) the other features of the plasma lipoprotein profile. The APOE genotype exerted only a weak effect on the CEC via the modulation of the lipoprotein profile. The APOE locus was associated with omega-3 fatty acid levels independent of the plasma cholesterol level. Full article
(This article belongs to the Special Issue Lipids in Neurodegenerative Disorders)
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23 pages, 3859 KiB  
Article
Identification of Side Chain Oxidized Sterols as Novel Liver X Receptor Agonists with Therapeutic Potential in the Treatment of Cardiovascular and Neurodegenerative Diseases
by Na Zhan, Boyang Wang, Nikita Martens, Yankai Liu, Shangge Zhao, Gardi Voortman, Jeroen van Rooij, Frank Leijten, Tim Vanmierlo, Folkert Kuipers, Johan W. Jonker, Vincent W. Bloks, Dieter Lütjohann, Marcella Palumbo, Francesca Zimetti, Maria Pia Adorni, Hongbing Liu and Monique T. Mulder
Int. J. Mol. Sci. 2023, 24(2), 1290; https://doi.org/10.3390/ijms24021290 - 9 Jan 2023
Cited by 6 | Viewed by 2459
Abstract
The nuclear receptors—liver X receptors (LXR α and β) are potential therapeutic targets in cardiovascular and neurodegenerative diseases because of their key role in the regulation of lipid homeostasis and inflammatory processes. Specific oxy(phyto)sterols differentially modulate the transcriptional activity of LXRs providing opportunities [...] Read more.
The nuclear receptors—liver X receptors (LXR α and β) are potential therapeutic targets in cardiovascular and neurodegenerative diseases because of their key role in the regulation of lipid homeostasis and inflammatory processes. Specific oxy(phyto)sterols differentially modulate the transcriptional activity of LXRs providing opportunities to develop compounds with improved therapeutic characteristics. We isolated oxyphytosterols from Sargassum fusiforme and synthesized sidechain oxidized sterol derivatives. Five 24-oxidized sterols demonstrated a high potency for LXRα/β activation in luciferase reporter assays and induction of LXR-target genes APOE, ABCA1 and ABCG1 involved in cellular cholesterol turnover in cultured cells: methyl 3β-hydroxychol-5-en-24-oate (S1), methyl (3β)-3-aldehydeoxychol-5-en-24-oate (S2), 24-ketocholesterol (S6), (3β,22E)-3-hydroxycholesta-5,22-dien-24-one (N10) and fucosterol-24,28 epoxide (N12). These compounds induced SREBF1 but not SREBP1c-mediated lipogenic genes such as SCD1, ACACA and FASN in HepG2 cells or astrocytoma cells. Moreover, S2 and S6 enhanced cholesterol efflux from HepG2 cells. All five oxysterols induced production of the endogenous LXR agonists 24(S)-hydroxycholesterol by upregulating the CYP46A1, encoding the enzyme converting cholesterol into 24(S)-hydroxycholesterol; S1 and S6 may also act via the upregulation of desmosterol production. Thus, we identified five novel LXR-activating 24-oxidized sterols with a potential for therapeutic applications in neurodegenerative and cardiovascular diseases. Full article
(This article belongs to the Special Issue Lipids in Neurodegenerative Disorders)
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Review

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23 pages, 2478 KiB  
Review
Sphingolipid Players in Multiple Sclerosis: Their Influence on the Initiation and Course of the Disease
by Maria Podbielska, Toshio Ariga and Anna Pokryszko-Dragan
Int. J. Mol. Sci. 2022, 23(10), 5330; https://doi.org/10.3390/ijms23105330 - 10 May 2022
Cited by 13 | Viewed by 2904
Abstract
Sphingolipids (SLs) play a significant role in the nervous system, as major components of the myelin sheath, contributors to lipid raft formation that organize intracellular processes, as well as active mediators of transport, signaling and the survival of neurons and glial cells. Alterations [...] Read more.
Sphingolipids (SLs) play a significant role in the nervous system, as major components of the myelin sheath, contributors to lipid raft formation that organize intracellular processes, as well as active mediators of transport, signaling and the survival of neurons and glial cells. Alterations in SL metabolism and content are observed in the course of central nervous system diseases, including multiple sclerosis (MS). In this review, we summarize the current evidence from studies on SLs (particularly gangliosides), which may shed new light upon processes underlying the MS background. The relevant aspects of these studies include alterations of the SL profile in MS, the role of antibodies against SLs and complexes of SL-ligand-invariant NKT cells in the autoimmune response as the core pathomechanism in MS. The contribution of lipid-raft-associated SLs and SL-laden extracellular vesicles to the disease etiology is also discussed. These findings may have diagnostic implications, with SLs and anti-SL antibodies as potential markers of MS activity and progression. Intriguing prospects of novel therapeutic options in MS are associated with SL potential for myelin repair and neuroprotective effects, which have not been yet addressed by the available treatment strategies. Overall, all these concepts are promising and encourage the further development of SL-based studies in the field of MS. Full article
(This article belongs to the Special Issue Lipids in Neurodegenerative Disorders)
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