Association of blood lipids with onset and prognosis of amyotrophic lateral sclerosis: results from the ALS Swabia registry DOI Creative Commons
Sebastian Michels,

Deborah Kurz,

Angela Rosenbohm

et al.

Journal of Neurology, Journal Year: 2023, Volume and Issue: 270(6), P. 3082 - 3090

Published: Feb. 28, 2023

Abstract Background To date, the role of blood lipid levels and their association with onset prognosis ALS is controversial. We explored these associations in a large, population-based case–control study. Methods Between October 2010 June 2014, 336 patients (mean age 65.7 ± 10.7; 57.7% male) 487 sex- age-matched controls from same geographic region were recruited within registry Southwest Germany. Triglycerides cholesterol (high-density lipoprotein (HDL), low-density (LDL), total) measured. The cohort was followed up for vital status. Conditional logistic regression models applied to calculate odds ratio (OR) risk associated serum concentrations. In only, survival used appraise prognostic value. Results High concentration total (OR 1.60, 95% confidence interval (CI) 1.03–2.49, top vs. bottom quartile), but not HDL, LDL, LDL–HDL ratio, or triglycerides, positively ALS. During median follow-up time 88.9 months, 291 deaths occurred among patients. adjusted analysis, higher HDL (HR 1.72, CI 1.19–2.50) LDL 1.58, 1.11–2.26) mortality contrast, triglyceride lower 0.68, 0.48–0.96). Conclusion results highlight importance distinguish triglycerides when considering metabolism It further strengthens rationale triglyceride-rich diet, while negative impact must be explored.

Language: Английский

Multi-omic approach characterises the neuroprotective role of retromer in regulating lysosomal health DOI Creative Commons
James L. Daly,

Chris M. Danson,

Philip A. Lewis

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: May 29, 2023

Retromer controls cellular homeostasis through regulating integral membrane protein sorting and transport by controlling maturation of the endo-lysosomal network. dysfunction, which is linked to neurodegenerative disorders including Parkinson's Alzheimer's diseases, manifests in complex phenotypes, though precise nature this its relation neurodegeneration, remain unclear. Here, we perform an integrated multi-omics approach provide insight into impact dysfunction on health within a human neuroglioma cell model. We quantify widespread changes lysosomal proteome, indicative broad inefficient autophagic lysosome reformation, coupled with reconfigured surface proteome secretome reflective increased exocytosis. Through global proteomic parallel transcriptomic analysis, holistic view function emphasise role neuroprotection.

Language: Английский

Citations

25
Mangiferin alleviated poststroke cognitive impairment by modulating lipid metabolism in cerebral ischemia/reperfusion rats DOI
Hui Zhang,

Laifa Wang,

Xueqin Wang

et al.

European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 977, P. 176724 - 176724

Published: June 6, 2024

Language: Английский

Citations

10
Cholesterol imbalance and neurotransmission defects in neurodegeneration DOI Creative Commons
Kyung Chul Shin,

Houda Yasmine Ali Moussa,

Yongsoo Park

et al.

Experimental & Molecular Medicine, Journal Year: 2024, Volume and Issue: 56(8), P. 1685 - 1690

Published: Aug. 1, 2024

The brain contains the highest concentration of cholesterol in human body, which emphasizes importance physiology. Cholesterol is involved neurogenesis and synaptogenesis, age-related reductions levels can lead to synaptic loss impaired plasticity, potentially contribute neurodegeneration. maintenance homeostasis neuronal plasma membrane essential for normal function, imbalances distribution are associated with various neurodegenerative disorders, including Alzheimer's disease, Parkinson's Huntington's disease. This review aims explore molecular pathological mechanisms by imbalance neurotransmission defects neurodegeneration, focusing on four key mechanisms: (1) dysfunction, (2) alterations structure protein clustering, (3) oligomers amyloid beta (Aβ) protein, (4) α-synuclein aggregation.

Language: Английский

Citations

9
Cholesterol Metabolism in CNS Diseases: The Potential of SREBP2 and LXR as Therapeutic Targets DOI Creative Commons

N Wang,

Peng Sun,

Qi-Qi Shen

et al.

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 7, 2025

Language: Английский

Citations

1
Statin use and dementia risk: A systematic review and updated meta‐analysis DOI Creative Commons
Fernando Luiz Westphal Filho,

Paulo Roberto Moss Lopes,

Artur Menegaz de Almeida

et al.

Alzheimer s & Dementia Translational Research & Clinical Interventions, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 1, 2025

Language: Английский

Citations

1
Joint effect of modifiable risk factors on Parkinson’s disease: a large-scale longitudinal study DOI Creative Commons
Panlong Li,

Xirui Zhu,

Min Liu

et al.

Frontiers in Human Neuroscience, Journal Year: 2025, Volume and Issue: 19

Published: Jan. 27, 2025

Introduction Previous researches have often underestimated the diversity and combined effects of risk factors for Parkinson’s disease (PD). This study aimed to identify how multiple modifiable collectively impact PD. Methods The included 452,492 participants from UK Biobank, utilizing genetic data 255 phenotypic variables. A broad exposure association was conducted across seven domains: socioeconomic status, medical history, psychosocial factors, physical measures, early life, local environment, lifestyle. Risk scores each domain participant were generated. joint risks assessed using Cox proportional hazards model. Population attributable fraction (PAF) estimated quantify contribution ratio in different domains occurrence Results Multiple significantly ( p < 1.96 × 10 −4 ) associated with PD observed. top 5 hand grip strength (hazard (HR) = 0.98, 1.59 −24 ), long-standing illness (HR 1.38, 3.63 −20 self-reported nervousness 1.56, 5.9 ever suffered mental health concerns 1.42, 5.48 −18 chest pain 1.43 ). Individuals unfavorable lifestyle had an increased by 33 51% compared those favorable 0.001). Discussion indicated that addressing especially measures psychological could potentially prevent up 33.87% cases. In formulating prevention strategies, it is recommended prioritize such as lifestyle, history.

Language: Английский

Citations

1
Liver Fibrosis Associated with More Severe Motor Deficits in Early Parkinson’s Disease DOI
Aryeh Zolin,

Hwai Ooi,

Manqi Zhou

et al.

Clinical Neurology and Neurosurgery, Journal Year: 2025, Volume and Issue: unknown, P. 108861 - 108861

Published: March 1, 2025

Language: Английский

Citations

1
Altered Cholesterol Homeostasis in Huntington’s Disease DOI Creative Commons
Radhia Kacher,

Coline Mounier,

Jocelyne Caboche

et al.

Frontiers in Aging Neuroscience, Journal Year: 2022, Volume and Issue: 14

Published: April 19, 2022

Huntington’s disease (HD) is an autosomal dominant genetic disorder caused by expansion of the CAG repeat in first exon Huntingtin’s gene. The associated neurodegeneration mainly affects striatum and cortex at early stages progressively spreads to other brain structures. Targeting HD its earlier under intense investigation. Numerous drugs were tested, with a rate success only 3.5% approved molecules used as symptomatic treatment. restoration cholesterol metabolism, which central homeostasis strongly altered HD, could be interesting disease-modifying strategy. Cholesterol essential membrane component nervous system (CNS); alterations have deleterious consequences on neuronal functions. levels several sterols, upstream cholesterol, are markedly decreased within mouse model. Transcription biosynthetic genes reduced cell models well post-mortem striatal cortical tissues from patients. Since dynamic metabolism complex, it establish best method target HD. Cholesterol, does not cross blood-brain-barrier, locally synthesized renewed brain. All types CNS synthesize during development but they progress through adulthood, neurons down-regulate their synthesis turn astrocytes for full supply. Cellular reflect balance between synthesis, uptake export, all integrated into context talk glial cells. In this review, we describe latest advances regarding role deregulation functions how determinant factor degeneration progression. pathways major mechanisms sterols regulated will described. From overview, discuss main clinical strategies manipulating CNS, reinstate proper

Language: Английский

Citations

36
Connecting the Dots Between Hypercholesterolemia and Alzheimer’s Disease: A Potential Mechanism Based on 27-Hydroxycholesterol DOI Creative Commons
Mingan Wu, Yingying Zhai,

Xiaoyi Liang

et al.

Frontiers in Neuroscience, Journal Year: 2022, Volume and Issue: 16

Published: April 7, 2022

Alzheimer’s disease (AD), the most common cause of dementia, is a complex and multifactorial involving genetic environmental factors, with hypercholesterolemia considered as one risk factors. Numerous epidemiological studies have reported positive association between AD serum cholesterol levels, experimental also provide evidence that elevated levels accelerate pathology. However, underlying mechanism accelerating pathogenesis not clear. Here, we review metabolism in brain focus on role oxysterols, aiming to reveal link AD. 27-hydroxycholesterol (27-OHC) major peripheral oxysterol flows into brain, it affects β-amyloid (Aβ) production elimination well influencing other pathogenic mechanisms Although potential established, cholesterol-lowering drugs show mixed results improving cognitive function. Nevertheless, target exocytosis conversion benefits Herbs natural compounds properties ameliorating cognition. Collectively, causative factor for AD, 27-OHC likely promote Drugs regulate are probably beneficial but more research needed unravel involved 27-OHC, which may lead new therapeutic strategies

Language: Английский

Citations

36
Cholesterol determines the cytosolic entry and seeded aggregation of tau DOI Creative Commons
Benjamin J. Tuck, Lauren V. C. Miller, Panagiotis Katsinelos

et al.

Cell Reports, Journal Year: 2022, Volume and Issue: 39(5), P. 110776 - 110776

Published: May 1, 2022

Assemblies of tau can transit between neurons, seeding aggregation in a prion-like manner. To accomplish this, must cross cell-limiting membranes, process that is poorly understood. Here, we establish assays for the study entry into cytosol as phenomenon distinct from uptake, real time, and at physiological concentrations. The pathway cell type specific and, highly sensitive to cholesterol. Depletion cholesterol transporter Niemann-Pick C1 or extraction membrane renders neurons permissive potentiates even low levels exogenous assemblies. Conversely, supplementation reduces almost completely blocks seeded aggregation. Our findings rate-limiting step demonstrate dysregulated cholesterol, feature several neurodegenerative diseases, by promoting assemblies interior.

Language: Английский

Citations

33