Role of fenofibrate in multiple sclerosis DOI Creative Commons
Ahmad Abulaban, Hayder M. Al‐kuraishy, Ali I. Al‐Gareeb

et al.

European journal of medical research, Journal Year: 2024, Volume and Issue: 29(1)

Published: Feb. 9, 2024

Abstract Multiple sclerosis (MS) is the most frequent inflammatory and demyelinating disease of central nervous system (CNS). The underlying pathophysiology MS destruction myelin sheath by immune cells. formation plaques, inflammation, injury neuronal characterizes its neuropathology. plaques are multiple focal regions demyelination disseminated in brain's white matter, spinal cords, deep grey cerebral cortex. Fenofibrate a peroxisome proliferative activated receptor alpha (PPAR-α) that attenuates reactions MS. inhibits differentiation Th17 inhibiting expression pro-inflammatory signaling. According to these findings, this review intended illuminate mechanistic immunoinflammatory role fenofibrate mitigating In conclusion, can attenuate neuropathology modulating different pathways, including oxidative stress, autophagy, mitochondrial dysfunction, inflammatory-signaling neuroinflammation.

Language: Английский

Single-cell mapping of lipid metabolites using an infrared probe in human-derived model systems DOI Creative Commons
Yeran Bai,

Carolina M. Camargo,

Stella M.K. Glasauer

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 8, 2024

Abstract Understanding metabolic heterogeneity is the key to uncovering underlying mechanisms of metabolic-related diseases. Current imaging studies suffer from limitations including low resolution and specificity, model systems utilized often lack human relevance. Here, we present a single-cell platform enable direct lipid metabolism with high specificity in various human-derived 2D 3D culture systems. Through incorporation an azide-tagged infrared probe, selective detection newly synthesized lipids cells tissue became possible, while simultaneous fluorescence enabled cell-type identification complex tissues. In proof-of-concept experiments, were directly visualized human-relevant among different cell types, mutation status, differentiation stages, over time. We identified upregulated progranulin-knockdown induced pluripotent stem their differentiated microglia cells. Furthermore, observed that neurons brain organoids exhibited significantly lower compared astrocytes.

Language: Английский

Citations

24
APOE traffics to astrocyte lipid droplets and modulates triglyceride saturation and droplet size DOI Creative Commons
Ian A. Windham, Alex E. Powers, Joey V. Ragusa

et al.

The Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 223(4)

Published: Feb. 9, 2024

The E4 variant of APOE strongly predisposes individuals to late-onset Alzheimer's disease. We demonstrate that in response lipogenesis, apolipoprotein E (APOE) astrocytes can avoid translocation into the endoplasmic reticulum (ER) lumen and traffic lipid droplets (LDs) via membrane bridges at ER-LD contacts. knockdown promotes fewer, larger LDs after a fatty acid pulse, which contain more unsaturated triglyceride pulse-chase. This LD size phenotype was rescued by chimeric targets only LDs. Like depletion, APOE4-expressing form small number large enriched triglyceride. Additionally, APOE4 cells exhibit impaired turnover increased sensitivity peroxidation. Our data indicate plays previously unrecognized role as an surface protein regulates composition. causes aberrant composition morphology. study contributes accumulating evidence with large, are sensitized peroxidation, could contribute disease risk.

Language: Английский

Citations

22
Fluorescent probes - illuminate the interplay network between lipid droplets and other organelles DOI
Jialu Yang,

Juan Ning,

Pengju Sun

et al.

Coordination Chemistry Reviews, Journal Year: 2024, Volume and Issue: 510, P. 215792 - 215792

Published: March 28, 2024

Language: Английский

Citations

19
Lipid Droplets and Neurodegeneration DOI
Keya Mallick,

Shuchismita Paul,

Sayani Banerjee

et al.

Neuroscience, Journal Year: 2024, Volume and Issue: 549, P. 13 - 23

Published: May 6, 2024

Language: Английский

Citations

17
Long-term high-fat diet consumption by mice throughout adulthood induces neurobehavioral alterations and hippocampal neuronal remodeling accompanied by augmented microglial lipid accumulation DOI

Hong Zhuang,

Xiuting Yao, Hong Li

et al.

Brain Behavior and Immunity, Journal Year: 2021, Volume and Issue: 100, P. 155 - 171

Published: Nov. 27, 2021

Language: Английский

Citations

77
The Role of Impaired Mitochondrial Dynamics in MFN2-Mediated Pathology DOI Creative Commons
Mashiat Zaman, Timothy E. Shutt

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: March 24, 2022

The Mitofusin 2 protein (MFN2), encoded by the

Language: Английский

Citations

69
APOΕ4 lowers energy expenditure in females and impairs glucose oxidation by increasing flux through aerobic glycolysis DOI Creative Commons
Brandon C. Farmer, Holden C. Williams, Nicholas A. Devanney

et al.

Molecular Neurodegeneration, Journal Year: 2021, Volume and Issue: 16(1)

Published: Sept. 6, 2021

Abstract Background Cerebral glucose hypometabolism is consistently observed in individuals with Alzheimer’s disease (AD), as well young cognitively normal carriers of the Ε4 allele Apolipoprotein E (APOE), strongest genetic predictor late-onset AD. While this clinical feature has been described for over two decades, mechanism underlying these changes cerebral metabolism remains a critical knowledge gap field. Methods Here, we undertook multi-omic approach by combining single-cell RNA sequencing (scRNAseq) and stable isotope resolved metabolomics (SIRM) to define metabolic rewiring across astrocytes, brain tissue, mice, human subjects expressing APOE4. Results Single-cell analysis tissue from mice APOE revealed E4-associated decreases genes related oxidative phosphorylation, particularly astrocytes. This shift was confirmed on level isotopic tracing 13 C-glucose E4 which showed decreased pyruvate entry into TCA cycle increased lactate synthesis. Metabolic phenotyping astrocytes elevated glycolytic activity, oxygen consumption, blunted flexibility, lower rate oxidation presence lactate. Together, cellular findings suggest an increase aerobic glycolysis (i.e. Warburg effect). To test whether phenomenon translated APOE4 humans, analyzed plasma metabolome middle-aged participants without allele, used indirect calorimetry measure whole body consumption energy expenditure. In line data E4-expressing female subgroup that striking decrease expenditure compared non-carriers. primarily driven exaggerated following dietary challenge. Further, stunted accompanied markedly carriers, pathway suggested glycolysis. Conclusions results astrocyte, system-level reprogramming APOE4, ‘Warburg like’ endophenotype observable females decades prior clinically manifest

Language: Английский

Citations

61
Isoform- and cell-state-specific lipidation of ApoE in astrocytes DOI
Karina Lindner,

Katharina Beckenbauer,

Larissa van Ek

et al.

Cell Reports, Journal Year: 2022, Volume and Issue: 38(9), P. 110435 - 110435

Published: March 1, 2022

Language: Английский

Citations

54
Fatty Acids: An Insight into the Pathogenesis of Neurodegenerative Diseases and Therapeutic Potential DOI Open Access
Diego Julián Vesga-Jiménez,

Cynthia Martin,

George E. Barreto

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(5), P. 2577 - 2577

Published: Feb. 25, 2022

One of the most common lipids in human body is palmitic acid (PA), a saturated fatty with essential functions brain cells. PA used by cells as an energy source, besides being precursor signaling molecules and protein tilting across membrane. Although plays physiological brain, its excessive accumulation leads to detrimental effects on cells, causing lipotoxicity. This mechanism involves activation toll-like receptors (TLR) nuclear factor kappa-light-chain-enhancer activated B (NF-κB) pathways, consequent release pro-inflammatory cytokines, increased production reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, autophagy impairment. Importantly, some cellular changes induced lead augmented susceptibility development Alzheimer’s Parkinson´s diseases. Considering complexity response intrinsic differences this review, we provide overview molecular different their possible relationships neurodegenerative diseases (NDs). Furthermore, propose use other acids, such oleic or linoleic acid, potential therapeutic approaches against NDs, these acids can counteract PA’s negative

Language: Английский

Citations

51
Role of Brain Liver X Receptor in Parkinson’s Disease: Hidden Treasure and Emerging Opportunities DOI Creative Commons

Saud A. Alnaaim,

Hayder M. Al‐kuraishy, Αθανάσιος Αλεξίου

et al.

Molecular Neurobiology, Journal Year: 2023, Volume and Issue: 61(1), P. 341 - 357

Published: Aug. 22, 2023

Abstract Parkinson’s disease (PD) is a neurodegenerative due to the degeneration of dopaminergic neurons (DNs) in substantia nigra (SN). The liver X receptor (LXR) involved different diseases. Therefore, objective present review was clarify possible role LXR PD neuropathology. LXRs are most common nuclear receptors transcription factors that regulate cholesterol metabolism and have pleiotropic effects, including anti-inflammatory effects reducing intracellular accumulation. highly expressed adult brain act as endogenous sensors for cholesterol. neuroprotective against development neuroinflammation diseases by inhibiting expression pro-inflammatory cytokines. play an essential mitigating neuropathology inflammatory signaling pathways, neuroinflammation, oxidative stress, mitochondrial dysfunction, enhancement BDNF signaling. In conclusion, LXRs, through regulating homeostasis, may be effectual PD. Also, inhibition node-like pyrin 3 (NLRP3) inflammasome factor kappa B (NF-κB) could effectively prevent Taken together, crucial associated DNs.

Language: Английский

Citations

28