A5015283879- Alzheimer's disease research and treatments
- Cholesterol and Lipid Metabolism
- Fatty Acid Research and Health
- Peroxisome Proliferator-Activated Receptors
- Antioxidant Activity and Oxidative Stress
- Nuclear Receptors and Signaling
- Genetics and Neurodevelopmental Disorders
- Retinoids in leukemia and cellular processes
- Drug Transport and Resistance Mechanisms
- Neuroblastoma Research and Treatments
- Vitamin D Research Studies
- Mitochondrial Function and Pathology
- Cancer, Hypoxia, and Metabolism
- Neuroscience and Neuropharmacology Research
- Diabetes and associated disorders
- Adipose Tissue and Metabolism
- Cholinesterase and Neurodegenerative Diseases
- Glycosylation and Glycoproteins Research
- Folate and B Vitamins Research
- Diet and metabolism studies
- Ion Channels and Receptors
- Endoplasmic Reticulum Stress and Disease
- Neuroinflammation and Neurodegeneration Mechanisms
- Pancreatic function and diabetes
- Diabetes Treatment and Management
Saarland University
2012-2024
Amyloid-β (Aβ), major constituent of senile plaques in Alzheimer's disease (AD), is generated by proteolytic processing the amyloid precursor protein (APP) β- and γ-secretase. Several lipids, especially cholesterol, are associated with AD. Phytosterols naturally occurring cholesterol plant equivalents, recently been shown to cross blood-brain-barrier accumulating brain. Here, we investigated effect most nutritional prevalent phytosterols on APP processing. In general, less amyloidogenic than...
Enhanced oxidative stress is a contributing factor in the pathogenesis of several neurodegenerative disorders such as Alzheimer´s disease. Beneficial effects have been demonstrated for medium-chain fatty acids (MCFAs) nutritionally administered triglycerides (MCTs) or coconut oil (CO). The observed on cognitive impairment are generally attributed to hepatic metabolism MCFAs, where resulting ketone bodies serve an alternate energy source compensate impaired glucose utilisation human brain....
Lipids play an important role as risk or protective factors in Alzheimer’s disease (AD). Previously it has been shown that plasmalogens, the major brain phospholipids, are altered AD. However, remained unclear whether plasmalogens themselves able to modulate amyloid precursor protein (APP) processing if reduced plasmalogen level is a consequence of Here we identify which human AD postmortem brains and investigate their impact on APP resulting Aβ production. All tested species showed...
Alzheimer's disease (AD) is characterized by an accumulation of Amyloid-β (Aβ), released sequential proteolytic processing the amyloid precursor protein (APP) β - and γ-secretase. Aβ peptides can aggregate, leading to toxic oligomers plaque formation. not only dependent on de novo synthesis but also degradation. Neprilysin (NEP) one major enzymes involved in Here we investigate molecular mechanism NEP regulation, which up now controversially discussed be affected APP itself. We found that...
Ninety percent of the elderly population has a vitamin D hypovitaminosis, and several lines evidence suggest that there might be potential causal link between Alzheimer's disease (AD) non-sufficient supply with D. However, mechanisms linking AD to have not been completely understood. The aim our study is elucidate impact 25(OH) D<sub>3</sub> on amyloid precursor protein processing in mice N2A cells utilizing very moderate physiological hypovitaminosis range 20-30% compared...
One of the main characteristics Alzheimer's disease (AD) is β-amyloid peptide (Aβ) generated by β- and &#947;-secretase processing amyloid precursor protein (APP). Previously it has been demonstrated that polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA), are associated with a reduced risk AD caused decreased Aβ production. However, in epidemiological studies nutritional approaches, outcomes DHA-dependent treatment were partially controversial. PUFAs very...
Omega-3 polyunsaturated fatty acids (PUFAs) have been proposed to be highly beneficial in Alzheimer's disease (AD). AD pathology is closely linked an overproduction and accumulation of amyloid-β (Aβ) peptides as extracellular senile plaques the brain. Total Aβ levels are not only dependent on its production by proteolytic processing amyloid precursor protein (APP), but also Aβ-clearance mechanisms, including Aβ-degrading enzymes. Here we show that omega-3 PUFAs eicosapentaenoic acid (EPA)...
Cleavage of amyloid precursor protein (APP) by β- and γ-secretase generates amyloid-β (Aβ) APP intracellular domain (AICD) peptides. Presenilin (PS) 1 or 2 is the catalytic component complex. Mitochondrial dysfunction an established phenomenon in Alzheimer's disease (AD), but causes role PS1, APP, APP's cleavage products this process are largely unknown. We studied effect these AD-associated molecules on mitochondrial features. Using cells deficient PSs expression, expressing human wild-type...
One of the characteristics Alzheimer´s disease (AD) is an increased amyloid load and enhanced level reactive oxidative species (ROS). Vitamin E has known beneficial neuroprotective effects, previously, some studies suggested that vitamin associated with a reduced risk AD due to its antioxidative properties. However, epidemiological nutritional approaches treatment are controversial. Here, we investigate effect α-tocotrienol, which belongs group E, on AD-relevant processes in neuronal cell...
Background: Gangliosides were found to be associated with Alzheimer's disease (AD). Here we addressed a potential function of γ-secretase (presenilin) dependent cleavage the amyloid-precursor-protein (APP) in regulation ganglioside de novo synthesis. Methods: To identify role and APP synthesis used presenilin (PS) deficient cells mouse brains, mutated PS as well transgenic mice AD post mortem brains. Changes glucosylceramide synthase (GCS) activity identified by incorporation radiolabeled...
The E vitamins are a class of lipophilic compounds including tocopherols, which have high antioxidative properties. Because the elevated lipid peroxidation and increased reactive oxidative species in Alzheimer's disease (AD) many attempts been made to slow down progression AD by utilizing action vitamin E. Beside mixed results these studies nothing is known about impact on mechanisms leading amyloid-β production degradation being responsible for plaque formation, one characteristic...
The accumulation of amyloid β-protein (Aβ) is one the major pathological hallmarks Alzheimer's disease. Insulin-degrading enzyme (IDE), a zinc-metalloprotease, key involved in Aβ degradation, which, addition to production, critical for homeostasis. Here, we demonstrate that saturated medium-chain fatty acids (MCFAs) increase total degradation whereas longer result an inhibition its effect which could not be detected IDE knock-down cells. Further analysis underlying molecular mechanism...
Abstract One of the major pathological hallmarks Alzheimer´s disease (AD) is an accumulation amyloid‐β (Aβ) in brain tissue leading to formation toxic oligomers and senile plaques. Under physiological conditions, a tightly balanced equilibrium between Aβ‐production ‐degradation necessary prevent Aβ‐accumulation. Here, we investigate molecular mechanism how insulin‐degrading enzyme (IDE), one Aβ‐degrading enzymes, regulated amyloid precursor protein (APP) processing Aβ‐degradation linked...
The neuroblastoma cell lines SH-SY5Y and Neuro2A are commonly utilized models in neurobiological research. DMEM supplemented with different nutrients 5–10% Fetal Calf Serum (FCS) is typically used for culturing these lines. During special treatments, a reduced FCS content often deployed to reduce cellular proliferation or the of bioactive compounds. impact reduction culture media on metabolic profile cells currently unknown. Using an Amplex Red Assay, this study showed that consumption...
Abstract The vanilloid capsaicin is a widely consumed spice, known for its burning and “hot” sensation through activation of TRPV1 ion-channels, but also to decrease oxidative stress, inflammation influence tau-pathology. Beside these positive effects, little about effects on amyloid-precursor-protein (APP) processing leading amyloid-β (Aβ), the major component senile plaques. Treatment neuroblastoma cells with capsaicinoids (24 hours, 10 µM) resulted in enhanced Aβ-production reduced...