A5055470380- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Extracellular vesicles in disease
- Neuroscience and Neuropharmacology Research
- Cholinesterase and Neurodegenerative Diseases
- Nuclear Receptors and Signaling
- Neurogenesis and neuroplasticity mechanisms
- Computational Drug Discovery Methods
- Sirtuins and Resveratrol in Medicine
- Autophagy in Disease and Therapy
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immune cells in cancer
- Lipid Membrane Structure and Behavior
- S100 Proteins and Annexins
- RNA regulation and disease
- Tryptophan and brain disorders
- Cellular transport and secretion
- Trace Elements in Health
- Spinal Cord Injury Research
- Circular RNAs in diseases
- Advanced Proteomics Techniques and Applications
- 14-3-3 protein interactions
- GDF15 and Related Biomarkers
- Protein Hydrolysis and Bioactive Peptides
University of California, Los Angeles
2014-2024
Foundation for Psychocultural Research
2011-2024
University of California, San Francisco
2024
VA Greater Los Angeles Healthcare System
2014
University of California, Riverside
2006-2008
<h3>Background:</h3> Fragile X syndrome (FXS) is the most common single gene inherited form of mental retardation, with behaviours at extreme autistic spectrum. Subjects FXS and fragile retardation knock out (<i>Fmr1</i> KO) mice, an animal model for FXS, have been shown to exhibit defects in dendritic spine maturation that may underlie cognitive behavioural abnormalities FXS. Minocycline a tetracycline analogue has used clinical trials stroke, multiple sclerosis several neurodegenerative...
Human apolipoprotein E (apoE) isoforms may differentially modulate amyloid-β (Aβ) levels. Evidence suggests physical interactions between apoE and Aβ are partially responsible for these functional effects. However, the apoE/Aβ complex is not a single static structure; rather, it defined by detection methods. Thus, literature results inconsistent difficult to interpret. An ELISA was developed measure soluble in single, quantitative method used address hypothesis that reduced levels of an...
Abstract The microtubule‐associated protein tau has primarily been associated with axonal location and function; however, recent work shows release from neurons suggests an important role for in synaptic plasticity. In our study, we measured levels of total using synaptosomes prepared cryopreserved human postmortem Alzheimer's disease (AD) control samples. Flow cytometry data show that a majority terminals are highly immunolabeled the antibody (HT7) both AD Immunoblots synaptosomal fractions...
Alzheimer’s disease (AD) is the most common cause of dementia, yet there no cure or diagnostics available prior to onset clinical symptoms. Extracellular vesicles (EVs) are lipid bilayer-delimited particles that released from almost all types cell. Genome-wide association studies have linked multiple AD genetic risk factors microglia-specific pathways. It plausible microglia-derived EVs may play a role in progression by contributing dissemination insoluble pathogenic proteins, such as tau...
Long-term potentiation (LTP) is an activity-dependent and persistent increase in synaptic transmission. Currently available techniques to measure LTP are time-intensive require highly specialized expertise equipment, thus not well suited for screening of multiple candidate treatments, even animal models. To expand facilitate the analysis LTP, here we use a flow cytometry-based method track chemically induced by detecting surface AMPA receptors isolated synaptosomes: fluorescence...
Synaptic transfer of tau has long been hypothesized from the human pathology pattern and demonstrated in vitro vivo, but precise mechanisms remain unclear. Extracellular vesicles such as exosomes have suggested a mechanism, not all is exosomal. The present experiments use novel flow cytometry assay to quantify depolarization synaptosomes by KCl after loading with FM2–10, which induces fluorescence reduction associated synaptic vesicle release; degree cryopreserved samples equaled that seen...
Dendritic spines are protrusions from the dendritic shaft that host most excitatory synapses in brain. Although they first emerge during neuronal maturation, remain plastic through adulthood, and recent advances molecular mechanisms governing spine morphology have shown them to be exquisitely sensitive changes micro-environment. Among many factors affecting components regulators of extracellular matrix (ECM). Modification ECM is critical repair injuries throughout body, including CNS. Matrix...
Endophilin-B1, also known as Bax-interacting factor 1 (Bif-1, and encoded by SH3GLB1), is a multifunctional protein involved in apoptosis, autophagy mitochondrial function. We recently described unique neuroprotective role for neuron-specific alternatively spliced isoforms of endophilin-B1. To examine whether endophilin-B1-mediated neuroprotection could be novel therapeutic target Alzheimer's disease we used double mutant amyloid precursor presenilin (APPswe/PSEN1dE9) mouse model observed...
Abstract We describe here the results from testing of a small molecule first-in-class apolipoprotein E4 (ApoE4)-targeted sirtuin1 (SirT1) enhancer, A03, that increases levels neuroprotective enzyme SirT1 while not affecting neurotoxic sirtuin 2 (SirT2) in vitro ApoE4-transfected cells. A03 was identified by high-throughput screening (HTS) and found to be orally bioavailable brain penetrant. In vivo , treatment increased hippocampus 5XFAD-ApoE4 (E4FAD) Alzheimer’s disease (AD) model mice...
We report the discovery of a novel class compounds that function as dual inhibitors enzymes neutral sphingomyelinase-2 (nSMase2) and acetylcholinesterase (AChE). Inhibition these provides unique strategy to suppress propagation tau pathology in treatment Alzheimer's disease (AD). describe key SAR elements affect relative nSMase2 and/or AChE inhibitor effects potency, addition identification two analogs release tau-bearing exosomes vitro vivo. Identification nSMase2/AChE represents new...
Abstract Aim We have previously reported that cambinol (DDL-112), a known inhibitor of neutral sphingomyelinase-2 (nSMase2), suppressed extracellular vesicle (EV)/exosome production in vitro cell model and reduced tau seed propagation. The enzyme nSMase2 is involved the exosomes carrying proteopathic seeds could contribute to cell-to-cell transmission pathological protein aggregates implicated neurodegenerative diseases such as Parkinson’s disease (PD). Here, we performed vivo studies...
The neuronal and gliaI populations within the brain are tightly interwoven, making isolation study of large a single cell type from tissue major technical challenge. Concurrently, cell-type specific extracellular vesicles (EVs) hold enormous diagnostic therapeutic potential in neurodegenerative disorders including Alzheimer's disease (AD). Postmortem AD cortical samples were thawed gently dissociated. Following filtration, myelin red blood removal, pellets immunolabeled with fluorescent...
Abstract Studies of mice lacking MHC class I (MHC I)-associated proteins have demonstrated a role for in neurodevelopment. A central question arising from these observations is whether neuronal recognition has specificity the allele product and peptide presented. Using well-established embryonic retina explant system, we observed that picomolar levels recombinant self-MHC molecule inhibited neurite outgrowth. We then assessed neurobiological activity panel soluble Is, consisting different...
Mice that are deficient in classical major histocompatibility complex class I (MHCI) have abnormalities synaptic plasticity and neurodevelopment more extensive loss of synapses reduced axon regeneration after sciatic nerve transection, suggesting MHCI participates maintaining regeneration. Little is known about the biological consequences up-regulating MHCI's expression on neurons. To understand neurobiological activity better, particular its role neurorepair injury, we studied a transgenic...