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      Sphingolipids as prognostic biomarkers of neurodegeneration, neuroinflammation, and psychiatric diseases and their emerging role in lipidomic investigation methods

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          Abstract

          Lipids play an important role in neurodegeneration, neuroinflammation, and psychiatric disorders and an imbalance in sphingolipid levels is associated with disease. Although early diagnosis and intervention of these disorders would clearly have favorable long-term outcomes, no diagnostic tests currently exist that can accurately identify people at risk. Reliable prognostic biomarkers that are easily accessible would be beneficial to determine therapy and treatment response in clinical trials. Recent advances in lipidomic investigation methods have greatly progressed the knowledge of sphingolipids in neurodegenerative and psychiatric disorders over the past decades although more longitudinal studies are needed to understand its exact role in these disorders to be used as potential tools in the clinic.

          In this review, we give an overview of the current knowledge of sphingolipids in neurodegenerative and psychiatric disorders and explore recent advances in investigation methods. Finally, the potential of sphingolipid metabolism products and signaling molecules as potential biomarkers for diagnosis, prognostic, or surrogate markers of treatment response is discussed.

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          Most cited references206

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          Parkinson's disease: clinical features and diagnosis.

          Parkinson's disease (PD) is a progressive neurological disorder characterised by a large number of motor and non-motor features that can impact on function to a variable degree. This review describes the clinical characteristics of PD with emphasis on those features that differentiate the disease from other parkinsonian disorders. A MedLine search was performed to identify studies that assess the clinical characteristics of PD. Search terms included "Parkinson's disease", "diagnosis" and "signs and symptoms". Because there is no definitive test for the diagnosis of PD, the disease must be diagnosed based on clinical criteria. Rest tremor, bradykinesia, rigidity and loss of postural reflexes are generally considered the cardinal signs of PD. The presence and specific presentation of these features are used to differentiate PD from related parkinsonian disorders. Other clinical features include secondary motor symptoms (eg, hypomimia, dysarthria, dysphagia, sialorrhoea, micrographia, shuffling gait, festination, freezing, dystonia, glabellar reflexes), non-motor symptoms (eg, autonomic dysfunction, cognitive/neurobehavioral abnormalities, sleep disorders and sensory abnormalities such as anosmia, paresthesias and pain). Absence of rest tremor, early occurrence of gait difficulty, postural instability, dementia, hallucinations, and the presence of dysautonomia, ophthalmoparesis, ataxia and other atypical features, coupled with poor or no response to levodopa, suggest diagnoses other than PD. A thorough understanding of the broad spectrum of clinical manifestations of PD is essential to the proper diagnosis of the disease. Genetic mutations or variants, neuroimaging abnormalities and other tests are potential biomarkers that may improve diagnosis and allow the identification of persons at risk.
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            Sphingosine-1-phosphate: an enigmatic signalling lipid.

            The evolutionarily conserved actions of the sphingolipid metabolite, sphingosine-1-phosphate (S1P), in yeast, plants and mammals have shown that it has important functions. In higher eukaryotes, S1P is the ligand for a family of five G-protein-coupled receptors. These S1P receptors are differentially expressed, coupled to various G proteins, and regulate angiogenesis, vascular maturation, cardiac development and immunity, and are important for directed cell movement.
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              Functional rafts in cell membranes.

              A new aspect of cell membrane structure is presented, based on the dynamic clustering of sphingolipids and cholesterol to form rafts that move within the fluid bilayer. It is proposed that these rafts function as platforms for the attachment of proteins when membranes are moved around inside the cell and during signal transduction.
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                Author and article information

                Journal
                8710523
                21484
                Adv Drug Deliv Rev
                Adv Drug Deliv Rev
                Advanced drug delivery reviews
                0169-409X
                1872-8294
                6 November 2020
                28 April 2020
                2020
                15 December 2020
                : 159
                : 232-244
                Affiliations
                [a ]Division of Neuroscience, School for Mental Health and Neuroscience, Faculty of Health, Medicine, and Life Sciences, Maastricht University, Maastricht, the Netherlands
                [b ]LIMES Institute for Membrane Biology and Lipid Biochemistry, Kekulé-Institute, University of Bonn, Bonn, Germany
                [c ]Department of Health Sciences Research and Department of Neurology, Mayo Clinic College of Medicine, Rochester, Minnesota, United States
                [d ]The Maastricht Multimodal Molecular Imaging Institute (M4I), Division of Imaging Mass Spectrometry, Maastricht University, Maastricht, the Netherlands
                [e ]Life and Health Sciences Research Institute (ICVS), ICVS/3B’s, School of Medicine, University of Minho, Braga, Portugal
                Author notes
                [1]

                Authors contributed equally to this paper.

                [* ]Corresponding author. p.martinez@ 123456maastrichtuniversity.nl (P. Martinez-Martinez).
                Article
                NIHMS1644309
                10.1016/j.addr.2020.04.009
                7665829
                32360155
                90ac192c-0d10-4389-91f0-195e4b7e26ca

                This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/).

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                Categories
                Article

                sphingolipids,neurodegeneration,neuroinflammation,psychiatric diseases,lipidomics,biomarkers,surrogate markers

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