Involvement of Sphingolipids in the Pathogenesis of Parkinson's Disease and Parkinsonism

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Biomacromolecules: Lipids".

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 18491

Special Issue Editors


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Guest Editor
Emanuel Institute of Biochemical Physics, Russian Academyof Sciences Moscow, Moscow, Russia
Interests: neurolipidology; sphingolipids; apoptosis; neuroinflammation; ALS; Alzheimer and Parkinson Deseases

Special Issue Information

Dear colleagues, 

Sphingolipids (SphLs) are essential molecules for the physiopathology of the brain. State-of-the-art enzymatic, microscopy, and sphingolipidomic studies have highlighted that sphingolipid pathway disfunctions may account for mood disorders, behavioral symptoms, promote inflammation, oxidative stress, and degeneration of the central nervous system. Inducible dysfunction of the SphLs metabolism is involved in the pathogenesis of Parkinson’s disease.  

This Special Issue welcomes the submission of original research papers or comprehensive reviews that demonstrate or summarize significant advances in the field of sphingolipids in pathogenesis of Parkinson’s disease and Parkinsonism. The papers may be devoted to recent studies which have shown that different SphLs play a decisive role in the pathogenesis of Parkinson’s disease through results obtained in vitro and in vivo, such as brain tissue from animals in which diseases were induced and in humans autopsy samples, liquor, and blood. Articles dealing with evidence that SphL species might be diagnostic markers and/or new targets for innovative therapeutic strategies are also welcome in this Special Issue. Critical reviews and discussion papers revealing problems and drawing future perspectives of the involvement of sphingolipids in pathogenesis of PD are especially invited.

Prof. Dr. Elisabetta Albi
Prof. Dr. Alice V. Alessenko
Guest Editors

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Keywords

  • Parkinson’s disease
  • Parkinsonism
  • sphingolipids
  • glucocerebrosidase

Published Papers (4 papers)

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Research

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19 pages, 2832 KiB  
Article
The Sphingolipid Asset Is Altered in the Nigrostriatal System of Mice Models of Parkinson’s Disease
by Victor Blokhin, Maria Shupik, Ulyana Gutner, Ekaterina Pavlova, Albert T. Lebedev, Olga Maloshitskaya, Vsevolod Bogdanov, Sergey Sokolov, Alice Alessenko and Michael Ugrumov
Biomolecules 2022, 12(1), 93; https://doi.org/10.3390/biom12010093 - 6 Jan 2022
Cited by 3 | Viewed by 2316
Abstract
Parkinson’s disease (PD) is a neurodegenerative disease incurable due to late diagnosis and treatment. Therefore, one of the priorities of neurology is to study the mechanisms of PD pathogenesis at the preclinical and early clinical stages. Given the important role of sphingolipids in [...] Read more.
Parkinson’s disease (PD) is a neurodegenerative disease incurable due to late diagnosis and treatment. Therefore, one of the priorities of neurology is to study the mechanisms of PD pathogenesis at the preclinical and early clinical stages. Given the important role of sphingolipids in the pathogenesis of neurodegenerative diseases, we aimed to analyze the gene expression of key sphingolipid metabolism enzymes (ASAH1, ASAH2, CERS1, CERS3, CERS5, GBA1, SMPD1, SMPD2, UGCG) and the content of 32 sphingolipids (subspecies of ceramides, sphingomyelins, monohexosylceramides and sphinganine, sphingosine, and sphingosine-1-phosphate) in the nigrostriatal system in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse models of the preclinical and clinical stages of PD. It has been shown that in PD models, the expression of five of the nine studied genes (CERS1, CERS5, ASAH1, ASAH2, and GBA1) increases but only in the substantia nigra (SN) containing dopaminergic cell bodies. Changes in the expression of enzyme genes were accompanied by an increase in the content of 7 of the 32 studied sphingolipids. Such findings suggest these genes as attractive candidates for diagnostic purposes for preclinical and clinical stages of PD. Full article
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Review

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9 pages, 4246 KiB  
Review
The Key Role of GM1 Ganglioside in Parkinson’s Disease
by Suman Chowdhury and Robert Ledeen
Biomolecules 2022, 12(2), 173; https://doi.org/10.3390/biom12020173 - 21 Jan 2022
Cited by 15 | Viewed by 3267
Abstract
We have endeavored in this review to summarize our findings, which point to a systemic deficiency of ganglioside GM1 in Parkinson’s disease (PD) tissues. These include neuronal tissues well known to be involved in PD, such as substantia nigra of the brain and [...] Read more.
We have endeavored in this review to summarize our findings, which point to a systemic deficiency of ganglioside GM1 in Parkinson’s disease (PD) tissues. These include neuronal tissues well known to be involved in PD, such as substantia nigra of the brain and those of the peripheral nervous system, such as the colon and heart. Moreover, we included skin and fibroblasts in the study as well as peripheral blood mononuclear cells; these are tissues not directly involved in neuronal signaling. We show similar findings for ganglioside GD1a, which is the metabolic precursor to GM1. We discuss the likely causes of these GM1 deficiencies and the resultant biochemical mechanisms underlying loss of neuronal viability and normal functioning. Strong support for this hypothesis is provided by a mouse PD model involving partial GM1 deficiency based on mono-allelic disruption of the B4galnt1 gene. We point out that progressive loss of GM1/GD1a occurs in the periphery as well as the brain, thus obviating the need to speculate PD symptom transfer between these tissues. Finally, we discuss how these findings point to a potential disease-altering therapy for PD:GM1 replacement, as is strongly implicated in animal studies and clinical trials. Full article
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14 pages, 898 KiB  
Review
The Multiple Roles of Sphingomyelin in Parkinson’s Disease
by Paola Signorelli, Carmela Conte and Elisabetta Albi
Biomolecules 2021, 11(9), 1311; https://doi.org/10.3390/biom11091311 - 5 Sep 2021
Cited by 25 | Viewed by 4145
Abstract
Advances over the past decade have improved our understanding of the role of sphingolipid in the onset and progression of Parkinson’s disease. Much attention has been paid to ceramide derived molecules, especially glucocerebroside, and little on sphingomyelin, a critical molecule for brain physiopathology. [...] Read more.
Advances over the past decade have improved our understanding of the role of sphingolipid in the onset and progression of Parkinson’s disease. Much attention has been paid to ceramide derived molecules, especially glucocerebroside, and little on sphingomyelin, a critical molecule for brain physiopathology. Sphingomyelin has been proposed to be involved in PD due to its presence in the myelin sheath and for its role in nerve impulse transmission, in presynaptic plasticity, and in neurotransmitter receptor localization. The analysis of sphingomyelin-metabolizing enzymes, the development of specific inhibitors, and advanced mass spectrometry have all provided insight into the signaling mechanisms of sphingomyelin and its implications in Parkinson’s disease. This review describes in vitro and in vivo studies with often conflicting results. We focus on the synthesis and degradation enzymes of sphingomyelin, highlighting the genetic risks and the molecular alterations associated with Parkinson’s disease. Full article
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23 pages, 1636 KiB  
Review
Ceramide Metabolism and Parkinson’s Disease—Therapeutic Targets
by Antía Custodia, Marta Aramburu-Núñez, Clara Correa-Paz, Adrián Posado-Fernández, Ana Gómez-Larrauri, José Castillo, Antonio Gómez-Muñoz, Tomás Sobrino and Alberto Ouro
Biomolecules 2021, 11(7), 945; https://doi.org/10.3390/biom11070945 - 25 Jun 2021
Cited by 32 | Viewed by 7644
Abstract
Ceramide is a bioactive sphingolipid involved in numerous cellular processes. In addition to being the precursor of complex sphingolipids, ceramides can act as second messengers, especially when they are generated at the plasma membrane of cells. Its metabolic dysfunction may lead to or [...] Read more.
Ceramide is a bioactive sphingolipid involved in numerous cellular processes. In addition to being the precursor of complex sphingolipids, ceramides can act as second messengers, especially when they are generated at the plasma membrane of cells. Its metabolic dysfunction may lead to or be a consequence of an underlying disease. Recent reports on transcriptomics and electrospray ionization mass spectrometry analysis have demonstrated the variation of specific levels of sphingolipids and enzymes involved in their metabolism in different neurodegenerative diseases. In the present review, we highlight the most relevant discoveries related to ceramide and neurodegeneration, with a special focus on Parkinson’s disease. Full article
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