Sphingomyelin in Lewy Inclusion Bodies in Parkinson's Disease

Jäger, W.

doi:10.1001/archneur.1969.00480180071006

Cited by 106 publications

(44 citation statements)

References 4 publications

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“…Instead, the focus has been on oligomerization and fibrillization into Lewy bodies. However, while αSyn is the predominant protein found in Lewy bodies, lipids are also present [182,183]. In fact, it was shown that lipids and αSyn colocalize to the periphery of isolated Lewy bodies.…”

Section: Discussionmentioning

confidence: 99%

Membrane remodeling and mechanics: Experiments and simulations of α-Synuclein

West

Brummel

Braun

et al. 2016

Biochimica et Biophysica Acta (BBA) - Biomembranes

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We review experimental and simulation approaches that have been used to determine curvature generation and remodeling of lipid bilayers by membrane-bending proteins. Particular emphasis is placed on the complementary approaches used to study α-Synuclein (αSyn), a major protein involved in Parkinson's disease (PD). Recent cellular and biophysical experiments have shown that the protein 1) deforms the native structure of mitochondrial and model membranes; and 2) inhibits vesicular fusion. Today's advanced experimental and computational technology has made it possible to quantify these protein-induced changes in membrane shape and material properties. Collectively, experiments, theory and multi-scale simulation techniques have established the key physical determinants of membrane remodeling and rigidity: protein binding energy, protein partition depth, protein density, and membrane tension. Despite the exciting and significant progress made in recent years in these areas, challenges remain in connecting biophysical insights to the cellular processes that lead to disease. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov.

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Section: Discussionmentioning

confidence: 99%

Membrane remodeling and mechanics: Experiments and simulations of α-Synuclein

West

Brummel

Braun

et al. 2016

Biochimica et Biophysica Acta (BBA) - Biomembranes

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“…α‐synuclein is an integral component of both brainstem‐type and cortical LBs . Lipids are also one of the components of brainstem‐type and cortical LBs . den Hartog Jager examined the substantia nigra and locus ceruleus from patients with PD using 17 different lipid staining techniques and demonstrated that LBs contain phospholipids, especially sphingomyelin .…”

Section: Discussionmentioning

confidence: 99%

“…24 Lipids are also one of the components of brainstem-type and cortical LBs. [12][13][14] den Hartog Jager examined the substantia nigra and locus ceruleus from patients with PD using 17 different lipid staining techniques and demonstrated that LBs contain phospholipids, especially sphingomyelin. 12 Issidorides et al also revealed that the core of LBs in the locus ceruleus showed reactivity for rhodamine B, which stains sphingolipids and sterols.…”

Section: Discussionmentioning

confidence: 99%

Isopentenyl diphosphate isomerase, a cholesterol synthesizing enzyme, is localized in Lewy bodies

et al. 2015

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Isopentenyl diphosphate isomerase (IDI) is a cytoplasmic enzyme involved in the biosynthesis of isoprenoids including cholesterols. IDI has two isoforms in humans: IDI1 and IDI2. Since lipids are known to be a component of Lewy bodies (LBs), we investigated the immunohistochemical localization of IDI1 and IDI2 in the brain of patients with LB disease and multiple system atrophy (MSA) and normal control subjects. In normal controls, the cytoplasm of neurons was weakly immunostained with anti-IDI1 and anti-IDI2 antibodies throughout the nervous system. In LB disease, brainstem-type LBs were strongly positive for IDI1 and IDI2, and cortical LBs were unstained or barely immunolabeled. Double immunofluorescence staining revealed co-localization of phosphorylated α-synuclein with IDI1 or IDI2. Glial cytoplasmic inclusions in MSA were unstained. Previous studies have shown that levels of cholesterol metabolites are increased in the cerebral cortex of patients with LB disease, and that these metabolites accelerate α-synuclein aggregation. The present findings suggest that IDI1 and IDI2 may be associated with the production of cholesterol metabolites in neurons, leading to α-synuclein aggregation during the process of LB formation.

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“…Furthermore, lipids are located in the core of brainstem‐type LBs and are diffusely distributed in cortical LBs 86–88 . Mitochondria are also observed in the presumably early stage of cortical and brainstem‐type LBs 88,144 .…”

Section: Molecular Components Of Lewy Bodiesmentioning

confidence: 99%

The Lewy body in Parkinson's disease: Molecules implicated in the formation and degradation of α‐synuclein aggregates

et al. 2007

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The histological hallmark of Parkinson's disease (PD) is the presence of fibrillar aggregates called Lewy bodies (LBs). LB formation has been considered to be a marker for neuronal degeneration, because neuronal loss is found in the predilection sites for LBs. To date, more than 70 molecules have been identified in LBs, in which alpha-synuclein is a major constituent of LB fibrils. Alpha-synuclein immunohistochemistry reveals that diffuse cytoplasmic staining develops into pale bodies via compaction, and that LBs arise from the peripheral portion of pale bodies. This alpha-synuclein abnormality is found in 10% of pigmented neurons in the substantia nigra and more than 50% of those in the locus ceruleus in PD. Recent studies have suggested that oligomers and protofibrils of alpha-synuclein are cytotoxic, and that LBs may represent a cytoprotective mechanism in PD.

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Sphingomyelin in Lewy Inclusion Bodies in Parkinson's Disease

Cited by 106 publications

References 4 publications

Membrane remodeling and mechanics: Experiments and simulations of α-Synuclein

Membrane remodeling and mechanics: Experiments and simulations of α-Synuclein

Isopentenyl diphosphate isomerase, a cholesterol synthesizing enzyme, is localized in Lewy bodies

The Lewy body in Parkinson's disease: Molecules implicated in the formation and degradation of α‐synuclein aggregates

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