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Neurolipids 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 May 2022) | Viewed by 3373

Special Issue Editor

Department of Pharmacology, School of Medicine and Nursery, Universidad del País Vasco / Euskal Herriko Unibersitatea, Leioa, Spain
Interests: neuropharmacology; neurolipids; cannabinoid; cholinergic; imaging mass spectrometry; Alzheimer’s disease; radioligand binding; neurodegeneration
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Special Issue Information

The lipid molecules that constitute most of the dry mass of brain are mainly phospholipids (PL), sphingolipids (SL) and cholesterol, which are located at cellular membranes. During the last decade new analytical methods have been developed allowing the description, localization and identification of these lipid molecules. Accordingly, the super specialization of lipids in the brain is being uncovered, accounting for a wide range of functions, that include their known structural, metabolic and energetic metabolism, but also some lipid species are being identified as lipid mediators and signalling agents. These lipids with signalling activity reach their maximum level of specialization and diversity in the Central Nervous System (CNS), where they can act as neuromodulators or real neurotransmitters involved in the control of multiple physiological processes. These endogenous lipid-based signalling molecules constitute complete neurotransmitter systems and can be denominated as neurolipids (in a similar way to the term “neuropeptides”). The main sources of neurolipids are membrane lipid precursors which are mobilized by phospholipases, sphingomyelinases or different hydroxylases. The identified neurolipids would include endocannabinoids, lysophospholipids (LP), some free fatty acids, platelet activating factors, some sulfatides-derived neurolipids such as ceramide, ceramide 1-phosphate, sphingosine, sphingosine 1-phosphate (S1P), but also some cholesterol-derived lipid mediators, as 24- and 25-hydroxycholesterols. The neurolipids can be autocrine or paracrine mediators participating in multiple physiological functions, such as cell proliferation, differentiation, cell migration, inflammation and apoptosis, but also in the development of different pathologies. Other neurotransmitter systems such as glutamatergic, γ-aminobutyric acid (GABA)ergic, dopaminergic or cholinergic system are modulating their synthesis and can be metabolized both enzymatically and non-enzymatically by oxidative degradation. Different G protein-coupled receptors (GPCR) for neurolipids have been identified and some GPCR orphan receptors could also be their target.

These neurolipid systems are very abundant, active and ubiquitously distributed in the different brain nucleus and cell types, including glial cells. Consequently, neurolipid systems are being analysed as powerful new therapeutic targets for the treatment of neurological diseases, including neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s diseases, or multiple sclerosis. This Special Issue aims to collect the most advanced results in the promising neurolipid field applied to the development of new therapeutic approaches for neurodegenerative diseases.

Dr. Rafael Rodriguez-Puertas
Guest Editor

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Keywords

  • Cannabinoid
  • Lysophospholipids
  • sphingosine 1 phosphate
  • lysophosphatidic acid
  • neurolipids
  • neurodegenerative diseases
  • Alzheimer’s disease
  • Parkinson’s disease
  • Hungtinton Chorea
  • Multiple sclerosis

Published Papers (1 paper)

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Research

22 pages, 4731 KiB  
Article
Modulation of Neurolipid Signaling and Specific Lipid Species in the Triple Transgenic Mouse Model of Alzheimer’s Disease
by Estibaliz González de San Román, Alberto Llorente-Ovejero, Jonatan Martínez-Gardeazabal, Marta Moreno-Rodríguez, Lydia Giménez-Llort, Iván Manuel and Rafael Rodríguez-Puertas
Int. J. Mol. Sci. 2021, 22(22), 12256; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222212256 - 12 Nov 2021
Cited by 9 | Viewed by 2286
Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia in aging populations. Recently, the regulation of neurolipid-mediated signaling and cerebral lipid species was shown in AD patients. The triple transgenic mouse model (3xTg-AD), harboring βAPPSwe, [...] Read more.
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia in aging populations. Recently, the regulation of neurolipid-mediated signaling and cerebral lipid species was shown in AD patients. The triple transgenic mouse model (3xTg-AD), harboring βAPPSwe, PS1M146V, and tauP301L transgenes, mimics many critical aspects of AD neuropathology and progressively develops neuropathological markers. Thus, in the present study, 3xTg-AD mice have been used to test the involvement of the neurolipid-based signaling by endocannabinoids (eCB), lysophosphatidic acid (LPA), and sphingosine 1-phosphate (S1P) in relation to the lipid deregulation. [35S]GTPγS autoradiography was used in the presence of specific agonists WIN55,212-2, LPA and CYM5442, to measure the activity mediated by CB1, LPA1, and S1P1 Gi/0 coupled receptors, respectively. Consecutive slides were used to analyze the relative intensities of multiple lipid species by MALDI Mass spectrometry imaging (MSI) with microscopic anatomical resolution. The quantitative analysis of the astrocyte population was performed by immunohistochemistry. CB1 receptor activity was decreased in the amygdala and motor cortex of 3xTg-AD mice, but LPA1 activity was increased in the corpus callosum, motor cortex, hippocampal CA1 area, and striatum. Conversely, S1P1 activity was reduced in hippocampal areas. Moreover, the observed modifications on PC, PA, SM, and PI intensities in different brain areas depend on their fatty acid composition, including decrease of polyunsaturated fatty acid (PUFA) phospholipids and increase of species containing saturated fatty acids (SFA). The regulation of some lipid species in specific brain regions together with the modulation of the eCB, LPA, and S1P signaling in 3xTg-AD mice indicate a neuroprotective adaptation to improve neurotransmission, relieve the myelination dysfunction, and to attenuate astrocyte-mediated neuroinflammation. These results could contribute to identify new therapeutic strategies based on the regulation of the lipid signaling in familial AD patients. Full article
(This article belongs to the Special Issue Neurolipids in Neurodegenerative Disorders)
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