A5031116516- Alzheimer's disease research and treatments
- Fatty Acid Research and Health
- Cholesterol and Lipid Metabolism
- Diet and metabolism studies
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Eicosanoids and Hypertension Pharmacology
- Peroxisome Proliferator-Activated Receptors
- Drug Transport and Resistance Mechanisms
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Dementia and Cognitive Impairment Research
- Cancer, Lipids, and Metabolism
- Nutritional Studies and Diet
- Metabolomics and Mass Spectrometry Studies
- Mitochondrial Function and Pathology
- Glycosylation and Glycoproteins Research
- Lipid metabolism and disorders
- Advanced Glycation End Products research
- Folate and B Vitamins Research
- Liver Disease Diagnosis and Treatment
- Lipoproteins and Cardiovascular Health
- Hormonal Regulation and Hypertension
- Metabolism and Genetic Disorders
- Diabetes Treatment and Management
- Crystallization and Solubility Studies
- Menopause: Health Impacts and Treatments
University of Southern California
2016-2025
Keck Hospital of USC
2017-2024
Southern California University for Professional Studies
2015-2024
Keck Graduate Institute
2024
Kyoto University
2021
State Research Institute of Organic Chemistry and Technology
2021
Dalian University of Technology
2021
Henan Normal University
2021
Indian Institute of Technology Bombay
2021
Université Sultan Moulay Slimane
2021
The APOE ε4 allele is the strongest genetic risk factor for late-onset Alzheimer's disease (AD). ApoE protein aggregation plays a central role in AD pathology, including accumulation of β-amyloid (Aβ). Lipid-poor ApoE4 prone to aggregate and lipidating protects it from aggregation. mechanisms regulating vivo are surprisingly not known. lipidation controlled by activity ATP binding cassette A1 (ABCA1). ABCA1 recycling degradation regulated ADP-ribosylation 6 (ARF6). We found that promoted...
Past clinical trials of docosahexaenoic Acid (DHA) supplements for the prevention Alzheimer's disease (AD) dementia have used lower doses and been largely negative. We hypothesized that larger DHA are needed adequate brain bioavailability APOE4 is associated with reduced delivery eicosapentaenoic acid (EPA) to before onset cognitive impairment.
The prevalence of insulin resistance, metabolic syndrome, and cardiovascular disease is greatest in older obese patients, effective evidence-based treatment strategies are lacking. A prospective controlled study was conducted on 24 (65.5 ± 5.0 years) (body mass index, 34.3 5.2 kg/m2) adults with clinically diagnosed syndrome. We examined the effect exercise alone (EX) or combined moderate caloric restriction (−500 kcal, EX + CR) risk factors. Measures sensitivity assessed by euglycemic...
Higher dietary intake of the essential fatty acid docosahexaenoic (DHA) has been associated with better cognitive performance in several epidemiological studies. Animal and vitro studies also indicate that DHA prevents amyloid deposition brain.To determine association between serum levels, cerebral amyloidosis, volumes brain areas affected by Alzheimer disease.Cross-sectional analysis levels together measures (Pittsburgh Compound B index), volumes, neuropsychological testing scores from 61...
Background Animal and human studies indicate that ABCA1‐mediated cholesterol transport is important in Alzheimer's disease (AD). We hypothesized the efficiency of cerebrospinal fluid (CSF) to facilitate efflux would be reduced participants with mild cognitive impairment (MCI) or AD compared cognitively healthy participants. Methods Results CSF was collected from a cross‐sectional study (n=47) MCI (n=35) probable (n=26).The capacity mediate assessed using BHK cell line can induced express...
Abstract Background Apolipoprotein E ( APOE ) ɛ4 and low cerebrospinal fluid (CSF) amyloid-β42 (Aβ42) levels are predictors for developing Alzheimer’s disease (AD). The results of several studies indicate an interaction between docosahexaenoic acid (DHA) consumption cognitive outcomes by genotype. Our objective in the present study was to examine whether genotype CSF Aβ42 were associated with reduced delivery DHA Disease Cooperative Study-sponsored clinical trial. Methods Phospholipid...
Docosahexaenoic acid (DHA), eicosapentaenoic (EPA), and arachidonic (AA) play key roles in several metabolic processes relevant to Alzheimer's disease (AD) pathogenesis neuroinflammation. Carrying the APOEɛ4 allele (APOE4) accelerates omega-3 polyunsaturated fatty (PUFA) oxidation. In a pre-planned subgroup analysis of Disease Cooperative Study-sponsored DHA clinical trial, APOE4 carriers with mild probable AD had no improvements cognitive outcomes compared placebo, while APOE 4 non-carriers...
Abstract Background Apolipoprotein E4 ( APOE4 ) is associated with a greater response to neuroinflammation and the risk of developing late-onset Alzheimer’s disease (AD), but mechanisms for this association are not clear. The activation calcium-dependent cytosolic phospholipase A 2 (cPLA2) involved in inflammatory signaling elevated within plaques AD brains. relation between genotype cPLA2 activity known. Methods Mouse primary astrocytes, mouse human brain samples differing by APOE genotypes...
Abstract We propose the hypothesis that small high‐density lipoprotein (HDL) particles reduce risk of Alzheimer's disease (AD) by virtue their capacity to exchange lipids, affecting neuronal membrane composition and vascular synaptic functions. Concentrations HDLs in cerebrospinal fluid (CSF) plasma were measured 180 individuals ≥60 years age using ion mobility methodology. Small HDL concentrations CSF positively associated with performance three domains cognitive function independent...
Abstract Background Chronic neuroinflammation is one of the hallmarks late-onset Alzheimer’s disease (AD) dementia pathogenesis. Carrying apolipoprotein ε4 ( APOE4 ) allele has been associated with an accentuated response to brain inflammation and increases risk AD progression. Among signaling pathways, aberrant eicosanoid activation plays a prominent role in neurodegeneration. Methods Using brains from Religious Order Study (ROS), this study compared measures lipidome older persons...
Lumbar radiculopathy pain represents a major public health problem, with few effective long-term treatments. Preclinical neuropathic and postsurgical studies implicate the kinase adenosine monophosphate activated (AMPK) as potential pharmacological target for treatment of chronic conditions. Metformin, which acts via AMPK, is safe clinically available drug used in diabetes. Despite strong preclinical rationale, utility metformin therapeutic has not yet been studied humans. Our objective was...
The apolipoprotein E ɛ4 (APOE4) allele is the strongest genetic risk factor identified for developing Alzheimer's disease (AD). Among brain lipids, alteration in ω-3 polyunsaturated fatty acid docosahexaenoic (DHA) homeostasis implicated AD pathogenesis. APOE4 may influence both DHA metabolism and cognitive outcomes.Using positron emission tomography, regional incorporation coefficients (k*), rates of from plasma into using [1-11C]-DHA (J in), cerebral blood flow [15O]-water were measured 22...
The apoC-III proteoform containing two sialic acid residues (apoC-III2) has different in vitro effects on lipid metabolism compared with asialylated (apoC-III0) or the most abundant monosialylated (apoC-III1) proteoforms. Cross-sectional and longitudinal associations between plasma proteoforms (by mass spectrometric immunoassay) lipids were tested randomized clinical trials: ACT NOW, a study of pioglitazone subjects impaired glucose tolerance (n = 531), RACED 296), intensive glycemic control...
Abstract Background Cellular senescence, a hallmark of aging, has been implicated in Alzheimer’s disease (AD) pathogenesis. Cholesterol accumulation is known to drive cellular senescence; however, its underlying mechanisms are not fully understood. ATP-binding cassette transporter A1 (ABCA1) plays an important role cholesterol homeostasis, and expression trafficking altered APOE4 AD models. However, the ABCA1 senescence associated with remains unclear. Methods We examined association between...
Chronic neuroinflammation plays a key role in the progression of Alzheimer's disease (AD), and cytosolic calcium-dependent phospholipase A2 (cPLA2) enzyme is critical mediator inflammatory lipid signaling pathways. Here we investigate therapeutic potential novel cPLA2 inhibitors modulating AD. By leveraging giga-scale V-SYNTHES 2.0 virtual screening on-demand chemical space conducting two rounds optimization for potency selectivity, have identified BRI-50460, achieving an IC50 0.88 nM...
Background Synapses are essential for learning and memory, their loss predicts cognitive decline in Alzheimer's disease (AD). Synaptic is associated with excitotoxicity, neuroinflammation, amyloid-β, tau pathology, but the molecular mechanisms remain unclear. There an urgent need to identify new targets modify slow synaptic decline. This study examines if calcium-dependent phospholipase A2 (cPLA2) implicated AD loss. cPLA2 catalyzes membrane phospholipids release arachidonic acid, which can...
Background Peripheral nerve injury (PNI) results in a fundamental reorganization of the translational machinery injured peripheral such that protein synthesis is increased manner linked to enhanced mTOR and ERK activity. We have shown metformin treatment, which activates adenosine monophosphate-activated kinase (AMPK), reverses tactile allodynia translation following PNI. To gain better understanding how PNI changes proteome sciatic ascertain treatment may cause further change, we conducted...