Cholesterol metabolism: physiological versus pathological aspects in intracerebral hemorrhage DOI Creative Commons
Ruoyu Huang,

Qiuyu Pang,

Lexin Zheng

et al.

Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(4), P. 1015 - 1030

Published: April 3, 2024

Cholesterol is an important component of plasma membranes and participates in many basic life functions, such as the maintenance cell membrane stability, synthesis steroid hormones, myelination. plays a key role establishment central nervous system. The brain contains 20% whole body’s cholesterol, 80% which located within myelin. A huge number processes (e.g., sterol regulatory element-binding protein pathway liver X receptor pathway) participate regulation cholesterol metabolism via mechanisms that include biosynthesis, intracellular transport, efflux. Certain injuries or diseases involving crosstalk among above can affect normal to induce detrimental consequences. Therefore, we hypothesized cholesterol-related molecules pathways serve therapeutic targets for system diseases. Intracerebral hemorrhage most severe hemorrhagic stroke subtype, with high mortality morbidity. Historical levels are associated risk intracerebral hemorrhage. Moreover, secondary pathological changes after dysregulation, neuroinflammation, demyelination, multiple types programmed death. Intracellular accumulation has been found In this paper, review system, known disturbance hemorrhage, links between We also several possible constructive identified based on provide cholesterol-based perspectives reference those interested treatment

Language: Английский

Astrocyte contribution to dysfunction, risk and progression in neurodegenerative disorders DOI
Ashley N. Brandebura, Adrien Paumier, Tarik Seref Onur

et al.

Nature reviews. Neuroscience, Journal Year: 2022, Volume and Issue: 24(1), P. 23 - 39

Published: Oct. 31, 2022

Language: Английский

Citations

255
Beyond the GFAP-Astrocyte Protein Markers in the Brain DOI Creative Commons
Agnieszka M. Jurga, Martyna Paleczna, Justyna Kadłuczka

et al.

Biomolecules, Journal Year: 2021, Volume and Issue: 11(9), P. 1361 - 1361

Published: Sept. 14, 2021

The idea of central nervous system as one-man band favoring neurons is long gone. Now we all are aware that and neuroglia team players constant communication between those various cell types essential to maintain functional efficiency a quick response danger. Here, summarize discuss known new markers astroglial multiple functions, their natural heterogeneity, cellular interactions, aging disease-induced dysfunctions. This review focused on newly reported facts regarding astrocytes, which beyond the old stereotypes. We present an up-to-date list marker proteins used identify broad spectrum phenotypes related physiological pathological conditions. aim this help choose well-tailored for specific needs further experimental studies, precisely recognizing differential glial phenotypes, or diagnostic purposes. hope it will categorize structural diversity population ease clear readout future results.

Language: Английский

Citations

187
Cholesterol and Alzheimer’s Disease; From Risk Genes to Pathological Effects DOI Creative Commons
Femke M. Feringa, Rik van der Kant

Frontiers in Aging Neuroscience, Journal Year: 2021, Volume and Issue: 13

Published: June 24, 2021

While the central nervous system compromises 2% of our body weight, it harbors up to 25% body's cholesterol. Cholesterol levels in brain are tightly regulated for physiological function, but mounting evidence indicates that excessive cholesterol accumulates Alzheimer's disease (AD), where may drive AD-associated pathological changes. This seems especially relevant late-onset AD, as several major genetic risk factors functionally associated with metabolism. In this review we discuss different systems maintain metabolism healthy brain, and how dysregulation these processes can lead, or contribute to, disease. We will also AD-risk genes might impact downstream AD pathology. Finally, address outstanding questions field recent technical advances CRISPR/Cas9-gene editing induced pluripotent stem cell (iPSC)-technology aid study problems.

Language: Английский

Citations

167
ApoE Lipidation as a Therapeutic Target in Alzheimer’s Disease DOI Open Access
Maria Fe Lanfranco, Christi Anne S. Ng, G. William Rebeck

et al.

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(17), P. 6336 - 6336

Published: Sept. 1, 2020

Apolipoprotein E (APOE) is the major cholesterol carrier in brain, affecting various normal cellular processes including neuronal growth, repair and remodeling of membranes, synaptogenesis, clearance degradation amyloid β (Aβ) neuroinflammation. In humans, APOE gene has three common allelic variants, termed E2, E3, E4. APOE4 considered strongest genetic risk factor for Alzheimer’s disease (AD), whereas APOE2 neuroprotective. To perform its functions, apoE must be secreted properly lipidated, a process influenced by structural differences associated with isoforms. Here we highlight importance lipidated as well APOE-lipidation targeted therapeutic approaches that have potential to correct or prevent neurodegeneration. Many these been validated using diverse animal models. Overall, there great improve state goal ameliorating APOE-associated central nervous system impairments.

Language: Английский

Citations

138
Brain cell type-specific cholesterol metabolism and implications for learning and memory DOI
Dingfeng Li,

Juan Zhang,

Qiang Liu

et al.

Trends in Neurosciences, Journal Year: 2022, Volume and Issue: 45(5), P. 401 - 414

Published: Feb. 17, 2022

Language: Английский

Citations

88
The Relationship of Omega-3 Fatty Acids with Dementia and Cognitive Decline: Evidence from Prospective Cohort Studies of Supplementation, Dietary Intake, and Blood Markers DOI Creative Commons

Bao‐Zhen Wei,

Lin Li,

Cheng‐Wen Dong

et al.

American Journal of Clinical Nutrition, Journal Year: 2023, Volume and Issue: 117(6), P. 1096 - 1109

Published: April 5, 2023

Language: Английский

Citations

58
Acetyl-CoA Metabolism and Histone Acetylation in the Regulation of Aging and Lifespan DOI Creative Commons
Patrick C. Bradshaw

Antioxidants, Journal Year: 2021, Volume and Issue: 10(4), P. 572 - 572

Published: April 8, 2021

Acetyl-CoA is a metabolite at the crossroads of central metabolism and substrate histone acetyltransferases regulating gene expression. In many tissues fasting or lifespan extending calorie restriction (CR) decreases glucose-derived metabolic flux through ATP-citrate lyase (ACLY) to reduce cytoplasmic acetyl-CoA levels decrease activity p300 acetyltransferase (HAT) stimulating pro-longevity autophagy. Because this, compounds that have been described as CR mimetics. But few authors highlighted potential longevity promoting roles nuclear acetyl-CoA. For example, increasing increases acetylation administration class I deacetylase (HDAC) inhibitors increased acetylation. Therefore, likely plays an important role in longevity. Although synthetase 2 (ACSS2) promotes aging by decreasing autophagy some peripheral tissues, glial AMPK neuronal differentiation can stimulate ACSS2 translocation chromatin association. result CREB binding protein (CBP), p300/CBP-associated factor (PCAF), other HATs increase on promoter neuroprotective genes including transcription EB (TFEB) target resulting lysosomal biogenesis Much what known regarding has come from pioneering studies with yeast, fruit flies, nematodes. These identified evolutionary conserved for Future should focus control hypothalamic inflammation, driver organismal aging.

Language: Английский

Citations

101
Plasma lipidome is dysregulated in Alzheimer’s disease and is associated with disease risk genes DOI Creative Commons
Yue Liu, Anbupalam Thalamuthu, Karen A. Mather

et al.

Translational Psychiatry, Journal Year: 2021, Volume and Issue: 11(1)

Published: June 6, 2021

Abstract Lipidomics research could provide insights of pathobiological mechanisms in Alzheimer’s disease. This study explores a battery plasma lipids that can differentiate disease (AD) patients from healthy controls and determines whether lipid profiles correlate with genetic risk for AD. AD samples were collected the Sydney Memory Ageing Study (MAS) Sydney, Australia (aged range 75–97 years; 51.2% male). Untargeted lipidomics analysis was performed by liquid chromatography coupled–mass spectrometry (LC–MS/MS). We found several species nine classes, particularly sphingomyelins (SMs), cholesterol esters (ChEs), phosphatidylcholines (PCs), phosphatidylethanolamines (PIs), phosphatidylinositols triglycerides (TGs) are dysregulated may help discriminate them controls. However, when grouped together into subgroups, only DG group significantly higher ChEs, SMs, TGs resulted good classification accuracy using Glmnet algorithm (elastic net penalization generalized linear model [glm]) more than 80% AUC. In general, subclasses LPC PE had less compared to other subclasses. also significant increases PIs, LPE/PE ratio human U251 astroglioma cell lines exposed pathophysiological concentrations oligomeric Aβ 42 . suggests plays contributory, if not causal role, mediating changes be detected periphery. addition, we evaluated association AD-related single nucleotide polymorphisms (SNPs) polygenic scores (PRS) FERMT2 MS4A6A showed differential all classes across control groups. ABCA7 half (52.63%) PI (57.14%), respectively. Additionally, 43.4% SM class differentially associated CLU More 30% ChE, PE, TG associations separate genes (ChE- PICALM , SLC24A4 SORL1 ; PE- CR1 TG- BINI ) between group. These data renewed pathobiology feasibility identifying individuals greater risk.

Language: Английский

Citations

87
Plasma Lipids as Biomarkers for Alzheimer's Disease: A Systematic Review DOI Open Access

Mehak Agarwal,

Safeera Khan

Cureus, Journal Year: 2020, Volume and Issue: unknown

Published: Dec. 10, 2020

Alzheimer's disease (AD) is caused by several risk factors leading to dementia. It’s diagnosis usually depends on clinical presentation and certain biomarkers in the cerebrospinal fluid (CSF). The brain has a high content of cholesterol metabolism can be associated with beta-amyloid plaques formation, which seen Alzheimer’s disease. Given these implications, we studied if plasma lipid levels vary used as diagnose predict progression Certain mutations transport receptors proteins their association were also studied. This systematic review abides Preferred Reporting Items for Systematic Reviews Meta-Analyses (PRISMA) guidelines. We searched multiple databases, such Pubmed, Google Scholar, Pubmed central, ScienceDirect, Web Science, Medline help keywords like disease, cognitive impairment, biomarkers, cholesterol, separately combination each other. collected 49 quality appraised articles between lipids genetic alleles related applying inclusion exclusion criteria. Based finding studies reviewed, found an lipids, polymorphisms genes transport, Increased serum low-density lipoprotein (LDL-C), triglycerides (TG), total (TC), sphingolipids, 24S hydroxycholesterol (24S-HC), 27O (27O-HC) was Alzheimer's. Decreased high-density (HDL-C) phospholipids noticed. Genetic apolipoprotein E (ApoE), B (ApoB), A (ApoA), ATP binding cassette transporter 1 (ABCA1), 7 (ABCA7), amyloid precursor protein (APP), cytochrome P450 family 46 subfamilies member (CYP46A1), presenilin (PSEN1), 2 (PSEN2) are increased study Alzheimer's, proving that early It may prognosis stage severity. Further needed find out exact mechanism behind changes.

Language: Английский

Citations

72
Astrocytes as a Therapeutic Target in Alzheimer’s Disease–Comprehensive Review and Recent Developments DOI Open Access
Mateo Rodríguez-Giraldo, Rodrigo E. González-Reyes, Sofía Ramírez-Guerrero

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(21), P. 13630 - 13630

Published: Nov. 7, 2022

Alzheimer’s disease (AD) is a frequent and disabling neurodegenerative disorder, in which astrocytes participate several pathophysiological processes including neuroinflammation, excitotoxicity, oxidative stress lipid metabolism (along with critical role apolipoprotein E function). Current evidence shows that have both neuroprotective neurotoxic effects depending on the stage microenvironmental factors. Furthermore, appear to be affected by presence of amyloid-beta (Aβ), alterations calcium levels, gliotransmission proinflammatory activity via RAGE-NF-κB pathway. In addition, play an important tau clearance Aβ through glymphatic system. this review, we will discuss novel pharmacological non-pharmacological treatments focused as therapeutic targets for AD. These interventions include anti-inflammatory/antioxidant systems, glutamate activity, metabolism, neurovascular coupling system, dysregulation, release peptides affects glial neuronal function. According AD stage, these therapies may benefit either preventing or delaying progression disease.

Language: Английский

Citations

64