A5084082026- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Tryptophan and brain disorders
- Immune Response and Inflammation
- Neurological Disease Mechanisms and Treatments
- Neurotransmitter Receptor Influence on Behavior
- Molecular Sensors and Ion Detection
- S100 Proteins and Annexins
- Neuroscience and Neuropharmacology Research
- Mitochondrial Function and Pathology
- Chemokine receptors and signaling
- Protein Kinase Regulation and GTPase Signaling
- Endoplasmic Reticulum Stress and Disease
- Electrochemical sensors and biosensors
- Photoreceptor and optogenetics research
- Alcohol Consumption and Health Effects
- Epigenetics and DNA Methylation
- Diabetes and associated disorders
- Genetics and Neurodevelopmental Disorders
- Luminescence and Fluorescent Materials
- Autophagy in Disease and Therapy
- Molecular spectroscopy and chirality
- HIV Research and Treatment
- Biotin and Related Studies
- Analytical Chemistry and Sensors
University of New Mexico
2014-2025
Cleveland Clinic
2010-2012
Pathological aggregation of tau is a hallmark Alzheimer's disease and related tauopathies. We have previously shown that the deficiency microglial fractalkine receptor (CX3CR1) led to acceleration pathology memory impairment in an hTau mouse model tauopathy. Here, we show microglia drive cell-autonomous manner. First, hyperphosphorylation occur as early 2 months age hTauCx3cr1−/− mice. Second, CD45+ activation correlates with spatial deficit spread anatomically connected regions hippocampus....
Abstract Autophagy is a conserved homeostatic process active in all human cells and affecting spectrum of diseases. Here we use pharmaceutical screen to discover new mechanisms for activation autophagy. We identify subset pharmaceuticals inducing autophagic flux with effects diverse cellular systems modelling specific stages several diseases such as HIV transmission hyperphosphorylated tau accumulation Alzheimer’s disease. One drug, flubendazole, potent inducer autophagy initiation by...
Hyperphosphorylation and aggregation of tau protein are the pathological hallmarks Alzheimer's disease related tauopathies. We previously demonstrated that microglial activation induces hyperphosphorylation cognitive impairment via p38 mitogen-activated kinase (p38 MAPK) in hTau mouse model tauopathy was deficient for fractalkine receptor CX3CR1.We report an isoform-selective, brain-permeable, orally bioavailable small molecule inhibitor p38α MAPK (MW181) its effects on phosphorylation vitro...
Pathological hyperphosphorylation and aggregation of tau (pTau) neuroinflammation, driven by interleukin-1β (IL-1β), are the major hallmarks tauopathies.Here, we show that pTau primes activates IL-1β.First, RNA-sequence analysis suggests paired-helical filaments (PHFs)
Abstract INTRODUCTION Pathological accumulation of tau (pTau) contributes to various tauopathies, including Alzheimer's disease (AD), and correlates with cognitive decline. A rapid surge in tau‐targeted approaches via anti‐sense oligonucleotides, active/passive immunotherapies suggests that targeting p‐Tau is a viable strategy against tauopathies. METHOD We describe multi‐species validation our previously described Qß virus‐like particle (VLP)–based vaccine technology phosphorylated on...
Neuroinflammation is one of the neuropathological hallmarks Alzheimer's disease (AD) and related tauopathies. Activated microglia spatially coexist with microtubule-associated protein tau (Mapt or tau)-burdened neurons in brains human AD non-AD Numerous studies have suggested that neuroinflammation precedes pathology induction blockage via lipopolysaccharide (LPS) anti-inflammatory compounds (such as FK506) accelerate block pathology, respectively several animal models tauopathy. We...
Abstract With increased research funding for Alzheimer’s disease (AD) and related disorders across the globe, large amounts of data are being generated. Several studies employed machine learning methods to understand ever-growing omics enhance early diagnosis, map complex networks, or uncover potential drug targets. We describe results based on a Target Central Resource Database protein knowledge graph evidence paths transformed into vectors by metapath matching. extracted features between...
Abstract Tauopathies, including frontotemporal dementia (FTD) and Alzheimer’s disease (AD) are progressive neurodegenerative diseases clinically characterized by cognitive decline could be caused the aggregation of hyperphosphorylated pathological tau (pTau) as neurofibrillary tangles (NFTs) inside neurons. There is currently no FDA-approved treatment that cures, slows or prevents tauopathies. Current immunotherapy strategies targeting pTau have generated encouraging data but may pose...
Abstract Background Excessive alcohol (ethanol) consumption, such as binge drinking, is extremely commonplace and represents a major health concern. Through modeling excessive drinking in rodents, we are beginning to uncover the neurobiological neurobehavioral causes consequences of this pattern ethanol intake. One important factor for mice that they reliably drink blood concentrations (BECs) 80 mg/dl or higher. Drinking‐in‐the‐dark (DID) commonly used mouse model have shown method results...
Increasing evidence suggests that hyperphosphorylation and aggregation of microtubule-associated protein tau (MAPT or tau) correlates with the development cognitive impairment in Alzheimer's disease (AD) related tauopathies. While numerous attempts have been made to model AD-relevant pathology various animal models, there has very limited success for these models fully recapitulate progression as seen human Here, we performed whole genome gene expression a genomic mouse tauopathy expressed...
To determine the molecular basis and pathologic consequences of a chemically induced mutation in mouse model photoreceptor degeneration, nmf240.Mice from G3 N-ethyl-N-nitrosourea mutagenesis program were screened by indirect ophthalmoscopy for abnormal fundi. A chromosomal position recessive nmf240 was determined genome-wide linkage analysis use simple sequence length polymorphic markers an F2 intercross. The critical region refined, candidate genes direct sequencing. phenotype characterized...
Fractalkine (CX3CL1) and its receptor (CX3CR1) play an important role in regulating microglial function. We have previously shown that Cx3cr1 deficiency exacerbated tau pathology led to cognitive impairment. However, it is still unclear if the chemokine domain of ligand CX3CL1 essential neuronal pathology. used transgenic mice lacking endogenous Cx3cl1 (Cx3cl1−/−) expressing only obligatory soluble form (with domain) mucin stalk (referred as Cx3cl1105Δ mice) assess behavioral function both...
Tauopathies, including Alzheimer's disease (AD) and Frontotemporal Dementia (FTD), are histopathologically defined by the aggregation of hyperphosphorylated pathological tau (pTau) as neurofibrillary tangles in brain. Site-specific phosphorylation occurs early process correlates with progressive cognitive decline, thus serving targetable epitopes for immunotherapeutic development. Previously, we developed a vaccine (Qβ-pT181) displaying phosphorylated Thr181 peptides on surface Qβ...
The identification of protein aggregates as biomarkers for neurodegeneration is an area interest disease diagnosis and treatment development. In this work, we present novel super luminescent conjugated polyelectrolyte molecules ex vivo sensors tau-paired helical filaments (PHFs) amyloid-β (Aβ) plaques. We evaluated the use two oligo-p-phenylene ethynylenes (OPEs), anionic OPE12− cationic OPE24+, stains fibrillar pathology in brain sections transgenic mouse (rTg4510) rat (TgF344-AD) models...
Abstract Excessive alcohol (ethanol) consumption, such as binge-drinking, is extremely commonplace and represents a major health concern. Through modeling excessive drinking in rodents, we are beginning to uncover the neurobiological neurobehavioral causes consequences of this pattern ethanol intake. One important factor for binge mice that subjects reliably drink blood concentrations (BECs) 80 mg/dl or higher. Drinking-in-the-dark (DID) commonly used mouse model drinking, have shown these...
Tauopathies, including Alzheimer's disease (AD) and Frontotemporal Dementia (FTD), are histopathologically defined by the aggregation of hyperphosphorylated pathological tau (pTau) as neurofibrillary tangles in brain. Site-specific phosphorylation occurs early process correlates with progressive cognitive decline, thus serving targetable epitopes for immunotherapeutic development. Previously, we developed a vaccine (Qβ-pT181) displaying phosphorylated Thr181 peptides on surface Qβ...
Pathological aggregation of tau (pTau) and neuroinflammation, driven by interleukin-1β (IL-1β), are the major hallmarks tauopathies. Here, we show that pTau primes activates IL-1ß. First, burden correlates with increased IL-1β inflammasome proteins (NLRP3 ASC) in autopsy brains human Suppression blocks both priming activation ASC NLRP3 rTg4510 mouse model tauopathy. Treating microglia pTau-containing neuronal media, exosomes or purified tangles from tauopathy causes activation, which is...