A5102919267- Extracellular vesicles in disease
- Telomeres, Telomerase, and Senescence
- MicroRNA in disease regulation
- Cancer Genomics and Diagnostics
- Neuroinflammation and Neurodegeneration Mechanisms
- Alzheimer's disease research and treatments
- Genetics, Aging, and Longevity in Model Organisms
- Reproductive System and Pregnancy
- Autophagy in Disease and Therapy
- RNA Interference and Gene Delivery
- Circular RNAs in diseases
- Amyotrophic Lateral Sclerosis Research
- Advanced Nanomaterials in Catalysis
- Innovative Microfluidic and Catalytic Techniques Innovation
- Muscle Physiology and Disorders
- Phagocytosis and Immune Regulation
- DNA Repair Mechanisms
- Parkinson's Disease Mechanisms and Treatments
- Bioactive Compounds and Antitumor Agents
- bioluminescence and chemiluminescence research
- Multiple Sclerosis Research Studies
- Ocular Disorders and Treatments
- Long-Term Effects of COVID-19
- Lymphoma Diagnosis and Treatment
- Endoplasmic Reticulum Stress and Disease
National Institute on Aging
2013-2020
National Institutes of Health
2013-2020
Institute on Aging
2014-2019
Exosome Diagnostics (United States)
2017-2018
Ben-Gurion University of the Negev
2008-2016
Background Proteins pathogenic in Alzheimer's disease (AD) were extracted from neurally derived blood exosomes and quantified to develop biomarkers for the staging of sporadic AD. Methods Blood obtained at one time-point patients with AD (n = 57) or frontotemporal dementia (FTD) 16), two time-points others 24) when cognitively normal 1 10 years later diagnosed enriched neural sources by immunoabsorption. AD-pathogenic exosomal proteins enzyme-linked immunosorbent assays. Results Mean levels...
Our team has been a pioneer in harvesting extracellular vesicles (EVs) enriched for neuronal origin from peripheral blood and using them as biomarker discovery platform neurological disorders. This methodology demonstrated excellent diagnostic predictive performance Alzheimer's other neurodegenerative diseases multiple studies, providing strong proof of concept this approach. Here, we describe our detail offer further evidence that isolated EVs are origin. In addition, present represent more...
Efficient intercellular transfer of RNAs, proteins, and lipids as protected exosomal cargo has been demonstrated in the CNS, but distinct physiologic pathologic roles have not well defined for this pathway. The capacity to isolate immunochemically human plasma neuron-derived exosomes (NDEs), containing neuronspecific cargo, permitted characterization CNS-derived living humans. Constituents amyloid β-peptide (Aβ)42-generating system now are examined 2 sets neural cells by quantification...
Abstract Cells release lipid-bound extracellular vesicles (EVs; exosomes, microvesicles and apoptotic bodies) containing proteins, lipids RNAs into the circulation. Vesicles mediate intercellular communication between both neighboring distant cells. There is substantial interest in using EVs as biomarkers for age-related diseases including cancer, neurodegenerative, metabolic cardiovascular diseases. The majority of research focuses on identifying differences when comparing disease states...
Type 2 diabetes is a chronic age-associated degenerative metabolic disease that reflects relative insulin deficiency and resistance. Extracellular vesicles (EVs) (exosomes, microvesicles, apoptotic bodies) are small (30-400 nm) lipid-bound capable of shuttling functional proteins, nucleic acids, lipids as part intercellular communication systems. Recent studies in mouse models cell culture suggest EVs may modulate signaling. Here, we designed cross-sectional longitudinal cohorts euglycemic...
Blood biomarkers able to diagnose Alzheimer disease (AD) at the preclinical stage would enable trial enrollment when is potentially reversible. Plasma neuronal-enriched extracellular vesicles (nEVs) of patients with AD were reported exhibit elevated levels phosphorylated (p) tau, Aβ42, and insulin receptor substrate 1 (IRS-1).To validate nEV as predictors.This case-control study included longitudinal plasma samples from cognitively normal participants in Baltimore Longitudinal Study Aging...
Purpose: Blood-based liquid biopsies offer easy access to genomic material for molecular diagnostics in cancer. Commonly used cell-free DNA (cfDNA) originates from dying cells. Exosomal nucleic acids (exoNAs) originate living cells, which can better reflect underlying cancer biology.Experimental Design: Next-generation sequencing (NGS) was test exoNA, and droplet digital PCR (ddPCR) BEAMing were cfDNA BRAFV600, KRASG12/G13, EGFRexon19del/L858R mutations 43 patients with progressing advanced...
Fetal bovine serum (FBS) is the most widely used supplement for mammalian cell culture. It supports growth by providing nutrients, signals, and protection from stress. Attempts to develop serum-free media that support expansion same extent as serum-supplemented have not yet succeeded, suggesting FBS contains one or more as-yet-undefined factors. One potential vehicle delivery of factors cultured cells extracellular vesicles (EVs).EV-depleted human were generated 120,000g centrifugation, its...
Abstract Alzheimer’s disease (AD) is an age-related neurodegenerative disorder in which aggregation-prone neurotoxic amyloid β-peptide (Aβ) accumulates the brain. Extracellular vesicles (EVs), including exosomes, are small 50–150 nm membrane that have recently been implicated prion-like spread of self-aggregating proteins. Here we report EVs isolated from AD patient cerebrospinal fluid and plasma, plasma two mouse models, medium neural cells expressing familial presenilin 1 mutations,...
Abstract The mitochondrial free radical theory of aging suggests that accumulating oxidative damage to mitochondria and DNA (mtDNA) plays a central role in aging. Circulating cell‐free mtDNA (ccf‐mtDNA) isolated from blood may be biomarker disease. Extracellular vesicles (EVs) are small (30–400 nm), lipid‐bound capable shuttling proteins, nucleic acids, lipids as part intercellular communication systems. Here, we report portion ccf‐mtDNA plasma is encapsulated EVs. To address whether EV...
Amyloid-β1-42 (Aβ) peptide effects on human models of central nervous system (CNS)-patrolling macrophages (Ms) and CD4 memory T-cells (CD4-Tms) were investigated to examine immune responses Aβ in Alzheimer's disease. lipopolysaccharide (LPS) elicited similar M cytokine exosomal mRNA (ex-mRNA) responses. Aβ- LPS-stimulated Ms from 20 ≥65-yr-old subjects generated significantly more IL-1, TNF-α, IL-6, but not IL-8 or IL-12, ex-mRNAs for than matched 21- 45-yr-old subjects. CD4-Tm generation...
Summary Obesity, metabolic syndrome, and hyperleptinemia are associated with aging age‐associated diseases including prostate cancer. One experimental approach to inhibit tumor growth is reduce dietary protein intake hence levels of circulating amino acids. Dietary restriction ( PR ) increases insulin sensitivity suppresses cancer cell in animal models, providing a rationale for clinical trials. We sought demonstrate that biomarkers derived from plasma extracellular vesicles EV s) reflect...
Abstract Extracellular vesicles (EVs) are involved in intercellular communication and affect processes including immune antiviral responses. Blood serum, a common cell culture medium component, is replete with EVs must be depleted prior to EV-related experiments. The extent which depletion deplete non-EV particles incompletely understood, but serum associated reduced viability growth culture. Here, we examined whether by two methods affected HIV-1 replication. In lines, latency models,...
The TORC1 pathway is necessary for ribosomal biogenesis and initiation of protein translation. Furthermore, the differentiation Th1 Th17 cells requires activity. To investigate role in and/or more detail, we compared capacity naïve T from wild type p70(S6K1) knockout mice. Expression many genes associated with Th17-cell differentiation, such as IL17a, IL17f, IL-23R, were reduced In contrast, development Th1, Th2, Treg was unaffected absence . expression major transcription factor retinoic...
Free radical-mediated oxidative damage to proteins, lipids, and DNA occurs in neurons during acute brain injuries neurodegenerative disorders. Membrane lipid peroxidation contributes neuronal dysfunction death, part by disrupting ion homeostasis cellular bioenergetics. Emerging findings suggest that 4-hydroxynonenal (HNE), an aldehyde produced peroxidation, impairs the function of various proteins involved homeostasis. Here we tested hypothesis HNE system removes damaged organelles,...
Telomerase promotes tissue regeneration by delaying the entrance of cells into senescence. Studies performed on or animals overexpressing telomerase reverse transcriptase (TERT), catalytic subunit telomerase, have revealed that TERT exhibits antiapoptotic effects in neurons. However, it is not clear whether endogenous possesses these functions as well. Here we demonstrate presence active cytoplasm and nucleus cerebellar Purkinje neurons adult old mice. protein levels are reduced with age,...