Altered lipid profile and reduced neuronal support in human induced pluripotent stem cell‐derived astrocytes from adrenoleukodystrophy patients DOI Creative Commons
Roberto Montoro Ferrer, Yorrick R. J. Jaspers,

Inge M. E. Dijkstra

и другие.

Journal of Inherited Metabolic Disease, Год журнала: 2024, Номер 48(1)

Опубликована: Дек. 20, 2024

X-linked adrenoleukodystrophy (ALD) is a peroxisomal disorder resulting from pathogenic variants in the ABCD1 gene that primarily affects nervous system and characterized by progressive axonal degeneration spinal cord peripheral nerves leukodystrophy. Dysfunction of very long-chain fatty acid (VLCFA) degradation has been implicated ALD pathology, but impact on astrocytes, which critically support neuronal function, remains poorly understood. Fibroblasts four patients were reprogrammed to generate human-induced pluripotent stem cells (hiPSC). hiPSC-derived astrocytes generated study astrocytic homeostasis. Our reveals significant changes lipidome an enrichment VLCFAs across multiple lipid classes, including triacylglycerols, cholesteryl esters, phosphatidylcholines. Importantly, not only exhibit intrinsic dysregulation also affect dendritic tree complexity neurons co-culture systems. These findings highlight cell-autonomous effects protein their microenvironment, shed light potential mechanisms underlying neuropathology, underscore critical role health.

Язык: Английский

Impaired membrane lipids in ischemic stroke: a key player in inflammation and thrombosis DOI Creative Commons

Qian Wang,

Dandan Wang, Yan Gao

и другие.

Journal of Neuroinflammation, Год журнала: 2025, Номер 22(1)

Опубликована: Май 28, 2025

Abstract Background Membrane lipids play a crucial role in brain function and cell signalling, they serve as key biological substrates inflammatory responses, thrombosis, energy metabolism. Multiple clinical molecular evidences suggest that membrane are probably involved the pathogenesis of ischemic stroke (IS). However, current knowledge about lipid landscape its involvement IS pathophysiology is limited. Methods We performed untargeted lipidomic analysis on erythrocyte membranes from 56 patients 55 healthy controls. Integrated with gene expression weighted co-expression network analysis, we identified dysregulated signalling pathways their contributions to pathophysiology. Results A total 1392 were detected quantified. Our results revealed significant impairment homeostasis patients, characterized by marked reduction glycerophospholipids (GPLs) lysophospholipids (LPLs). Further indicated impaired primarily concentrated three disturbed pathways, including phospholipase A2-mediated GPL-LPL pathway, C-mediated inositol 1,4,5-trisphosphate/diglyceride sphingosine-1-phosphate (S1P)-S1P receptors pathway. Gene these inhibited during subacute phase IS. Furthermore, form highly interconnected collaboratively contributes inflammation thrombosis IS, thereby influencing progression prognosis disease. Conclusion findings reveal which implicates processes This research offers new insights into pathogenesis, potentially informing future monitoring therapeutic strategies.

Язык: Английский

Процитировано

0
Molecular mapping of neuronal architecture using STORM microscopy and new fluorescent probes for SMLM imaging DOI Creative Commons
Victor Breton, Paul Nazac, David Boulet

и другие.

Neurophotonics, Год журнала: 2024, Номер 11(01)

Опубликована: Март 8, 2024

Imaging neuronal architecture has been a recurrent challenge over the years, and localization of synaptic proteins is frequent in neuroscience. To quantitatively detect analyze structure synapses, we recently developed free SODA software to association pre postsynaptic proteins. fully take advantage spatial distribution analysis complex cells, such as neurons, also selected some new dyes for plasma membrane labeling. Using Icy plugin, could both conventional single molecule microscopy, giving access molecular map at nanoscale level. replace those distributions within three-dimensional (3D) shape, used MemBright probes 3D STORM decipher entire shape various dendritic spine types single-molecule resolution We report here example mask, but these tools have broader spectrum interest since they can be whatever or cellular type. Altogether with thus provide perfect toolkit nanometric context.

Язык: Английский

Процитировано

2
A fatty acid elongase complex regulates cell membrane integrity and septin‐dependent host infection by the rice blast fungus DOI Creative Commons
Jia Su,

Youpin Xu,

Mingliang Lei

и другие.

Molecular Plant Pathology, Год журнала: 2024, Номер 25(7)

Опубликована: Июль 1, 2024

Abstract Very‐long‐chain fatty acids (VLCFAs) regulate biophysical properties of cell membranes to determine growth and development eukaryotes, such as the pathogenesis rice blast fungus Magnaporthe oryzae . The acid elongase Elo1 regulates M. by modulating VLCFA biosynthesis. However, it remains unknown whether how associates with other factors biosynthesis in fungal pathogens. Here, we identified Ifa38, Phs1 Tsc13 interacting proteins proximity labelling associated on endoplasmic reticulum (ER) membrane control Targeted gene deletion mutants Δ ifa38 , phs1 tsc13 were all similarly impaired elo1 vegetative growth, conidial morphology, stress responses ER, wall membrane. These also displayed severe damage integrity failed organize septin ring that is essential for penetration peg formation pathogenicity. Our study demonstrates employs a complex VLCFAs maintaining or remodelling structure, which important septin‐mediated host penetration.

Язык: Английский

Процитировано

2
Enzymes of sphingolipid metabolism as transducers of metabolic inputs DOI
Fabiola N. Velázquez,

Chiara Luberto,

Daniel Canals

и другие.

Biochemical Society Transactions, Год журнала: 2024, Номер 52(4), С. 1795 - 1808

Опубликована: Авг. 5, 2024

Sphingolipids (SLs) constitute a discrete subdomain of metabolism, and they display both structural signaling functions. Accumulating evidence also points to intimate connections between intermediary metabolism SL metabolism. Given that many SLs exhibit bioactive properties (i.e. transduce signals), these raise the possibility an important function is relay information on metabolic changes into specific cell responses. This could occur at various levels. Some metabolites are incorporated SLs, whereas others may initiate regulatory or events that, in turn, modulate In this review, we elaborate former as it represents poorly appreciated aspect develop hypothesis network highly sensitive several changes, focusing amino acids (serine alanine), fatty acids, choline (and ethanolamine), glucose.

Язык: Английский

Процитировано

2
Sex-Dependent Variations in Hypothalamic Fatty Acid Profile and Neuropeptides in Offspring Exposed to Maternal Obesity and High-Fat Diet DOI Open Access
Mayara da Nóbrega Baqueiro, Laís Angélica de Paula Simino, João Costa

и другие.

Nutrients, Год журнала: 2024, Номер 16(3), С. 340 - 340

Опубликована: Янв. 24, 2024

Maternal obesity and/or high-fat diet (HF) consumption can disrupt appetite regulation in their offspring, contributing to transgenerational and metabolic diseases. As fatty acids (FAs) play a role regulation, we investigated the maternal fetal levels of FAs as potential contributors programmed hyperphagia observed offspring obese dams. Female mice were fed either control (CT) or HF prior mating, blood tissues collected at 19 days gestation. Elevated linoleic acid serum dams well fetuses. An increased concentration eicosadienoic was also detected hypothalamus female HF-O male fetuses showed hypothalamic neuropeptide Y (Npy) gene expression, while decreased pro-opiomelanocortin (POMC) protein content. Both exhibited reduced neurogenin 3 (NGN-3) expression. In vitro experiments confirmed that LA contributed expression Pomc Ngn-3 neuronal cells. During lactation, consumed more milk had higher body weight compared CT. summary, this study demonstrated exposure during gestation alters FA composition hypothalamus, particularly increasing n-6, which may switch from POMC NPY neurons, leading gain lactation.

Язык: Английский

Процитировано

1
Is cholesterol both the lock and key to abnormal transmembrane signals in Autism Spectrum Disorder? DOI Creative Commons
Clifford A. Lingwood

Lipids in Health and Disease, Год журнала: 2024, Номер 23(1)

Опубликована: Апрель 20, 2024

Disturbances in cholesterol homeostasis have been associated with ASD. Lipid rafts are central many transmembrane signaling pathways (including mTOR) and changes raft content affect their order function. Cholesterol levels controlled by several mechanisms, including endoplasmic reticulum degradation (ERAD) of the rate limiting HMGCoA reductase. A new approach to increase via temporary ERAD blockade using a benign bacterial toxin-derived competitor for translocon is suggested.A lock key model cholesterol/lipid dependent proposed which provide both afferent efferent 'tumblers' across membrane allow 'lock key' receptor signals.

Язык: Английский

Процитировано

1
Identification of z‐axis filopodia in growth cones using super‐resolution microscopy DOI
Motohiro Nozumi, Y. SATO,

Miyako Nishiyama‐Usuda

и другие.

Journal of Neurochemistry, Год журнала: 2024, Номер unknown

Опубликована: Июль 1, 2024

A growth cone is a highly motile tip of an extending axon that crucial for neural network formation. Three-dimensional-structured illumination microscopy, type super-resolution light microscopy with resolution overcomes the optical diffraction limitation (ca. 200 nm) conventional well suited studying molecular dynamics intracellular events. Using this technique, we discovered novel filopodia distributed along z-axis ("z-filopodia") within cone. Z-filopodia were typically oriented in direction growth, not attached to substratum, protruded spontaneously without microtubule invasion, and had lifetime was considerably shorter than filopodia. formation regulated by actin-regulatory proteins, such as vasodilator-stimulated phosphoprotein, fascin, cofilin. Chromophore-assisted laser inactivation cofilin induced rapid turnover z-filopodia. An guidance receptor, neuropilin-1, concentrated z-filopodia transported together them, whereas its ligand, semaphorin-3A, selectively bound them. Membrane domains associated also specialized resembled those lipid rafts, their behaviors closely related neuropilin-1. The results suggest have unique properties, unlike xy-filopodia, do function force-generating structures extension.

Язык: Английский

Процитировано

1
Altered lipid profile and reduced neuronal support in human induced pluripotent stem cell‐derived astrocytes from adrenoleukodystrophy patients DOI Creative Commons
Roberto Montoro Ferrer, Yorrick R. J. Jaspers,

Inge M. E. Dijkstra

и другие.

Journal of Inherited Metabolic Disease, Год журнала: 2024, Номер 48(1)

Опубликована: Дек. 20, 2024

X-linked adrenoleukodystrophy (ALD) is a peroxisomal disorder resulting from pathogenic variants in the ABCD1 gene that primarily affects nervous system and characterized by progressive axonal degeneration spinal cord peripheral nerves leukodystrophy. Dysfunction of very long-chain fatty acid (VLCFA) degradation has been implicated ALD pathology, but impact on astrocytes, which critically support neuronal function, remains poorly understood. Fibroblasts four patients were reprogrammed to generate human-induced pluripotent stem cells (hiPSC). hiPSC-derived astrocytes generated study astrocytic homeostasis. Our reveals significant changes lipidome an enrichment VLCFAs across multiple lipid classes, including triacylglycerols, cholesteryl esters, phosphatidylcholines. Importantly, not only exhibit intrinsic dysregulation also affect dendritic tree complexity neurons co-culture systems. These findings highlight cell-autonomous effects protein their microenvironment, shed light potential mechanisms underlying neuropathology, underscore critical role health.

Язык: Английский

Процитировано

0