ReviewEssays in biochemistry2021
Membrane lipid raft homeostasis is directly linked to neurodegeneration.
Review in Essays in biochemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 36 citations in OpenAlex.
- Meta-inflammation through the lens of macrophage programming and nutrient-sensing ghrelin signaling.Immunometabolism (Cobham, Surrey) · 2026Review
- Circulating lipids uncover early membrane disruption as a primary event preceding Alzheimer's disease onset.Research square · 2026Article
- Article
- Review
- Untargeted Lipidomic Reveals Potential Biomarkers in Plasma Samples for the Discrimination of Patients Affected by Parkinson's Disease.Molecules (Basel, Switzerland) · 2025Article
- The Association Between Markers of Lipid Homeostasis, Inflammation, and Atherosclerosis Index in Patients with Type 2 Diabetes and Coronary Heart Disease Stratified by Glycemic Control: A Cross-Sectional Study.Journal of inflammation research · 2025Article
- Gut microbiota-host lipid crosstalk in Alzheimer's disease: implications for disease progression and therapeutics.Molecular neurodegeneration · 2024Review
- Cholesterol Levels, Hormone Replacement Therapy, and Incident Dementia among Older Adult Women.Nutrients · 2023Article
- Rafting on the Evidence for Lipid Raft-like Domains as Hubs Triggering Environmental Toxicants' Cellular Effects.Molecules (Basel, Switzerland) · 2023Review
- DHCR24 reverses Alzheimer's disease-related pathology and cognitive impairment via increasing hippocampal cholesterol levels in 5xFAD mice.Acta neuropathologica communications · 2023Article
- Cytomembrane Trafficking Pathways of Connexin 26, 30, and 43.International journal of molecular sciences · 2023Review
- Involvement of Lipids in the Pathogenesis of Amyotrophic Lateral Sclerosis.Life (Basel, Switzerland) · 2023Review
- Mysterious sphingolipids: metabolic interrelationships at the center of pathophysiology.Frontiers in physiology · 2023Review
- Pathogenesis of α-Synuclein in Parkinson's Disease: From a Neuron-Glia Crosstalk Perspective.International journal of molecular sciences · 2022Review
- Metabolome-wide association study onProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Amyloid β, Lipid Metabolism, Basal Cholinergic System, and Therapeutics in Alzheimer's Disease.International journal of molecular sciences · 2022Review
- The Role of Sphingomyelin and Ceramide in Motor Neuron Diseases.Journal of personalized medicine · 2022Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Age-associated neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and Alzheimer's disease (AD) are an unmet health need, with significant economic and societal implications, and an ever-increasing prevalence. Membrane lipid rafts (MLRs) are specialised plasma membrane microdomains that provide a platform for intracellular trafficking and signal transduction, particularly within neurons. Dysregulation of MLRs leads to disruption of neurotrophic signalling and excessive apoptosis which mirrors the final common pathway for neuronal death in ALS, PD and AD. Sphingomyelinase (SMase) and phospholipase (PL) enzymes process components of MLRs and therefore play central roles in MLR homeostasis and in neurotrophic signalling. We review the literature linking SMase and PL enzymes to ALS, AD and PD with particular attention to attractive therapeutic targets, where functional manipulation has been successful in preclinical studies. We propose that dysfunction of these enzymes is upstream in the pathogenesis of neurodegenerative diseases and to support this we provide new evidence that ALS risk genes are enriched with genes involved in ceramide metabolism (P=0.019, OR = 2.54, Fisher exact test). Ceramide is a product of SMase action upon sphingomyelin within MLRs, and it also has a role as a second messenger in intracellular signalling pathways important for neuronal survival. Genetic risk is necessarily upstream in a late age of onset disease such as ALS. We propose that manipulation of MLR structure and function should be a focus of future translational research seeking to ameliorate neurodegenerative disorders.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.