Involvement of Lipids in Alzheimer’s Disease Pathology and Potential Therapies

Frontiers in Physiology, Journal Year: 2020, Volume and Issue: 11

Published: June 9, 2020

Lipids constitute the bulk of dry mass brain and have been associated with healthy function as well most common pathological conditions brain. Demographic factors, genetics, lifestyles are major factors that influence lipid metabolism also key components disruption in Alzheimer's disease (AD). Additionally, genetic risk factor AD, APOE ϵ4 genotype, is involved transport metabolism. We propose lipids at center pathology based on their involvement blood-brain barrier function, amyloid precursor protein (APP) processing, myelination, membrane remodeling, receptor signaling, inflammation, oxidation, energy balance. Under conditions, homeostasis bestows a balanced cellular environment enables proper functioning cells. However, under dyshomeostasis composition can result disturbed BBB, abnormal processing APP, dysfunction endocytosis/exocytosis/autophagocytosis, altered unbalanced metabolism, enhanced inflammation. These disturbances may contribute to abnormalities hallmark AD. The wide variance suggest AD present complex interaction between several metabolic pathways augmented by such age, lifestyles. Herewith, we examine composition, review association all known facets pathology, offer pointers for potential therapies target pathways.

Language: Английский

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Shaping Neuronal Fate: Functional Heterogeneity of Direct Microglia-Neuron Interactions

Neuron, Journal Year: 2020, Volume and Issue: 109(2), P. 222 - 240

Published: Dec. 2, 2020

Language: Английский

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Can MRI measure myelin? Systematic review, qualitative assessment, and meta-analysis of studies validating microstructural imaging with myelin histology

NeuroImage, Journal Year: 2021, Volume and Issue: 230, P. 117744 - 117744

Published: Jan. 30, 2021

Recent years have seen an increased understanding of the importance myelination in healthy brain function and neuropsychiatric diseases. Non-invasive microstructural magnetic resonance imaging (MRI) holds potential to expand translate these insights basic clinical human research, but sensitivity specificity different MR markers is a subject debate. To consolidate current knowledge on topic, we perform systematic review meta-analysis studies that validate by combining it with myelin histology. We find meta-analytic evidence for correlations between various histology metrics from MRI modalities, including fractional anisotropy, radial diffusivity, macromolecular pool, magnetization transfer ratio, susceptibility longitudinal relaxation rate, not mean diffusivity. Meta-analytic correlation effect sizes range widely, R2 = 0.26 0.82. However, formal comparisons MRI-based are limited methodological variability, inconsistent reporting publication bias, thus preventing establishment single most sensitive strategy measure MRI. facilitate further progress, provide detailed characterisation evaluated as online resource. also share set 12 recommendations future validating putative MR-based deploying them vivo humans.

Language: Английский

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Schwann Cell Precursors; Multipotent Glial Cells in Embryonic Nerves

Frontiers in Molecular Neuroscience, Journal Year: 2019, Volume and Issue: 12

Published: March 26, 2019

The cells of the neural crest, often referred to as crest stem cells, give rise a number sub-lineages, one which is Schwann glial peripheral nerves. Crest transform adult through generation two well defined intermediate stages, cell precursors (SCP) in early embryonic nerves, and immature (iSch) late perinatal SCP are formed when enter nascent nerves form intimate relationships with axons, diagnostic feature cells. This involves large-scale changes gene expression, including activation established markers. Like glia CNS, radial glia, retain developmental multipotency contribute other crest-derived lineages during development. SCP, closely related termed boundary cap later stages lineage have all been implicated tumor initiating NF1 associated neurofibromas. iSch from process that appearance additional differentiation markers, autocrine survival circuits, cellular elongation, formation endoneurial connective tissue basal lamina. Finally, peri- post-natal reversibly induced by axon-associated signals myelin non-myelin review article discusses development detail describes large molecular signaling systems control

Language: Английский

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Oligodendroglial glycolytic stress triggers inflammasome activation and neuropathology in Alzheimer’s disease

Science Advances, Journal Year: 2020, Volume and Issue: 6(49)

Published: Dec. 4, 2020

The Drp1-HK1-NLRP3 axis is a key mechanism of oligodendrocyte damage and white matter degeneration in AD.

Language: Английский

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Transcriptional profiling of mouse peripheral nerves to the single-cell level to build a sciatic nerve ATlas (SNAT)

eLife, Journal Year: 2021, Volume and Issue: 10

Published: April 23, 2021

Peripheral nerves are organ-like structures containing diverse cell types to optimize function. This interactive assembly includes mostly axon-associated Schwann cells, but also endothelial cells of supporting blood vessels, immune system-associated barrier-forming the perineurium surrounding and protecting nerve fascicles, connective tissue-resident within intra-fascicular endoneurium inter-fascicular epineurium. We have established transcriptional profiles mouse sciatic nerve-inhabitant foster fundamental understanding peripheral nerves. To achieve this goal, we combined bulk RNA sequencing developing up adult with focused single-cell throughout postnatal development, extended by transcriptome analysis full both perinatally in adult. The results were merged resource Sciatic Nerve ATlas (SNAT: https://www.snat.ethz.ch ). anticipate that insights gained from our multi-layered will serve as valuable reference point guide future studies.

Language: Английский

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Schwann cell functions in peripheral nerve development and repair

Neurobiology of Disease, Journal Year: 2022, Volume and Issue: 176, P. 105952 - 105952

Published: Dec. 7, 2022

The glial cell of the peripheral nervous system (PNS), Schwann (SC), counts among most multifaceted cells body. During development, SCs secure neuronal survival and participate in axonal path finding. Simultaneously, they orchestrate architectural set up developing nerves, including blood vessels endo-, peri- epineurial layers. Perinatally, rodents, radially sort subsequently myelinate individual axons larger than 1 μm diameter, while small calibre become organised non-myelinating Remak bundles. have a vital role maintaining health throughout life several specialized SC types perform essential functions at specific locations, such as terminal neuromuscular junction (NMJ) or within cutaneous sensory end organs. In addition, neural crest derived satellite glia maintain tight communication with soma sensory, sympathetic, parasympathetic neurons derivatives are furthermore an indispensable part enteric system. remarkable plasticity becomes evident context nerve injury, where transdifferentiate into intriguing repair cells, which regenerative response that promotes repair. Indeed, multiple adaptations captivating, but remain often ill-resolved on molecular level. Here, we summarize discuss knowns unknowns vast array this single type can cover maintenance,

Language: Английский

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Overview of myelin, major myelin lipids, and myelin-associated proteins

Frontiers in Chemistry, Journal Year: 2023, Volume and Issue: 10

Published: Feb. 21, 2023

Myelin is a modified cell membrane that forms multilayer sheath around the axon. It retains main characteristics of biological membranes, such as lipid bilayer, but differs from them in several important respects. In this review, we focus on aspects myelin composition are peculiar to structure and differentiate it more conventional with special attention its constituent components most common proteins: basic protein, proteolipid protein zero. We also discuss many-fold functions myelin, which include reliable electrical insulation axons ensure rapid propagation nerve impulses, provision trophic support along axon organization unmyelinated nodes Ranvier, well relationship between biology neurologic disease multiple sclerosis. conclude brief history discovery field outline questions for future research.

Language: Английский

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Myelin insulation as a risk factor for axonal degeneration in autoimmune demyelinating disease

Nature Neuroscience, Journal Year: 2023, Volume and Issue: 26(7), P. 1218 - 1228

Published: June 29, 2023

Axonal degeneration determines the clinical outcome of multiple sclerosis and is thought to result from exposure denuded axons immune-mediated damage. Therefore, myelin widely considered be a protective structure for in sclerosis. Myelinated also depend on oligodendrocytes, which provide metabolic structural support axonal compartment. Given that pathology already visible at early disease stages, before overt demyelination, we reasoned autoimmune inflammation may disrupt oligodendroglial mechanisms hence primarily affect insulated by myelin. Here, studied as function myelination human mouse models encephalomyelitis with genetically altered myelination. We demonstrate ensheathment itself becomes detrimental survival increases risk degenerating an environment. This challenges view solely suggests dependence can become fatal when under inflammatory attack.

Language: Английский

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Oligodendrocytes: Myelination, Plasticity, and Axonal Support

Cold Spring Harbor Perspectives in Biology, Journal Year: 2024, Volume and Issue: 16(10), P. a041359 - a041359

Published: April 15, 2024

Mikael Simons1,2, Erin M. Gibson3 and Klaus-Armin Nave4 1Institute of Neuronal Cell Biology, Technical University Munich, Munich 80802, Germany 2German Center for Neurodegenerative Diseases, Cluster Systems Neurology (SyNergy), Institute Stroke Dementia Research, 81377, 3Department Psychiatry Behavioral Sciences, Stanford School Medicine, 94305, California, USA 4Department Neurogenetics, Max Planck Multidisciplinary Göttingen 37075, Correspondence: mikael.simons{at}dzne.de; egibson1{at}stanford.edu; nave{at}mpinat.mpg.de

Language: Английский

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