ATM (ataxia-telangiectasia mutated) is a PI3K-like kinase best known for its role in the DNA damage response (DDR), especially after double-strand breaks. Mutations gene result condition as ataxia-telangiectasia (A-T) that characterized by cancer predisposition, radiosensitivity, neurodegeneration, sterility, and acquired immune deficiency. We show here innate system not spared A-T. ATM-deficient microglia adopt an active phenotype includes overproduction of proinflammatory cytokines are...

ATM (ataxia telangiectasia mutated) protein is found associated with multiple organelles including synaptic vesicles, endosomes and lysosomes, often in cooperation ATR Rad3 related). Mutation of the gene results ataxia-telangiectasia (A-T), an autosomal recessive disorder defects organs nervous system. Precisely how deficiency leads to complex phenotypes A-T, however, remains elusive. Here, we reported that part connection may lie autophagy lysosomal abnormalities. We was degraded through...

The amyloid precursor protein (APP) is linked to the genetics and pathogenesis of Alzheimer's disease (AD). It parent β-amyloid (Aβ) peptide, main constituent plaques found in an AD brain. pathways from APP Aβ are intensively studied, yet normal functions itself have generated less interest. We report here that glutamate stimulation neuronal activity leads a rapid increase App gene expression. In mouse human neurons, elevated changes structure axon initial segment (AIS) where action...

Escherichia coli O157: H7 (EHEC) is a major foodborne pathogen largely transmitted to humans through the consumption of undercooked ground beef. This study investigated efficacy two food-grade, plant-derived antimicrobials, namely rutin (RT), and resveratrol (RV) with or without chitosan (CH) in enhancing EHEC inactivation hamburger patties. Further, effect aforementioned treatments on beef color lipid oxidation was analyzed. Additionally, deleterious effects these antimicrobial determined...

The amyloid precursor protein (APP) regulates neuronal excitability by altering the structure of axon initial segment. Using high density multielectrode arrays we compared electrophysiological consequences APP overexpression with exposure to β-amyloid (Aβ) and found that two manipulations affected neural activity in largely non-overlapping ways. In mature cultures (>18 days vitro, DIV18), reduced firing probability individual neurons, while stripped synapses impacting whole-network...

Inflammation plays a critical role in accelerating the progression of neurodegenerative diseases, such as Alzheimer's disease (AD) and ataxia telangiectasia (A-T). In A-T mouse models, LPS-induced neuroinflammation advances degenerative changes found cerebellar Purkinje neurons both vivo vitro. current study, we ask whether ibuprofen, non-steroidal anti-inflammatory drug (NSAID), can have opposite effect delay symptoms disease. We tested beneficial effects ibuprofen vitro models. Conditioned...

Adult-onset neurodegenerative diseases are often accompanied by evidence of a chronic inflammation that includes activation microglial cells and altered levels brain cytokines. Aspects this response likely secondary reactions to neurodegeneration, but for many illnesses the may itself be an early even causative disease event. In such cases, is referred as “sterile” it occurs in absence actual bacterial or viral pathogen. A potent trigger sterile CNS microglia has been shown presence DNA...

The expansion of urban areas and the increase in number buildings urbanization characteristics, such as roads, affect meteorological environment areas, resulting weakened pollutant dispersion. First, this paper uses GIS (geographic information system) spatial analysis technology landscape ecology methods to analyze dynamic changes land cover patterns Chengdu a result development. Second, most appropriate WRF (Weather Research Forecasting) model parameterization scheme is selected screened....

ABSTRACT White matter hyperintensity (WMH) is strongly correlated with age-related dementia and hypertension, but its pathogenesis remains obscure. GWAS identified TRIM47 at 17q25 locus as a top genetic risk factor for WMH formation. TRIM family class of E3 ubiquitin ligase pivotal functions in autophagy, which critical brain endothelial cell (ECs) remodeling during hypertension. We hypothesize that regulates autophagy loss-of-function disturbs cerebrovasculature. Based on transcriptomics...

Neuroinflammation is a common symptom of many neurodegenerative diseases, including Alzheimer's. It increasingly appreciated that chronic inflammation, even at low levels, creates pro-inflammatory environment major contributor to neuronal cell damage and hence the symptoms dementia. We previously showed DNA in microglia leads fragments "leaking" cytoplasm where they trigger STING-dependent sterile inflammation. In present study we ask whether astrocytes are also susceptible this...

Abstract Background The neurological symptom is highly related to the activation of innate immune system in brain neurodegenerative disease. robust microglia, which includes an overproduction cytokines, creates a pro‐inflammatory environment that greatly contributes neuronal cell damage. Method DNA damage was induced by either direct triggers double strands break or blocking repair. Conditioned media from microglia culture collected and treated culture. Different parameters, including...

Abstract The small Aβ peptide has been hypothesized to be the main driver of Alzheimer’s disease (AD). is a proteolytic cleavage product larger protein, amyloid precursor protein (APP), whose normal functions remain largely unexplored. We report here activities full-length APP that relate directly etiology AD. Increasing neuronal activity leads rapid increase in App gene expression. In both cultures mouse cortical neurons and human iPSC-derived neurons, elevated changes structure axon...

Abstract Background Alzheimer’s disease (AD) has a typical age of onset exceeding 65 years. The age‐dependency the condition led us to track appearance DNA damage in frontal cortex individuals who died with diagnosis AD. focus on was motivated by evidence that increasing levels irreparable are major driver aging process. This connection between and genomic integrity is compelling because also been identified as possible cause cellular senescence. number senescent cells increase ages, their...

Abstract Experiments in primary culture have helped advance our understanding of the curious phenomenon cell cycle-related neuronal death. In a differentiated postmitotic such as neuron, aberrant cycle reentry is strongly associated with apoptosis. Indeed, many pathologic conditions, populations at risk for death are marked by cells engaged like process. The evidence this conclusion typically based on finding MAP2 + that also positive proteins (e.g., cyclin D) or incorporated thymidine...

ABSTRACT Alzheimer’s disease (AD) is a neurodegenerative illness with typical age of onset exceeding 65 years age. The age-dependency the condition led us to track appearance DNA damage in frontal cortex individuals who died diagnosis AD. focus on was motivated by evidence that increasing levels irreparable are major driver aging process. connection between and loss genomic integrity compelling because has also been identified as possible cause cellular senescence. number senescent cells...

Alzheimer’s disease (AD) is a neurodegenerative illness with typical age of onset exceeding 65 years age. The dependency the condition led us to track appearance DNA damage in frontal cortex individuals who died diagnosis AD. focus on was motivated by evidence that increasing levels irreparable are major driver aging process. connection between and loss genomic integrity compelling because has also been identified as possible cause cellular senescence. number senescent cells reported...

Abstract White matter hyperintensity (WMH) is strongly correlated with age‐related dementia and hypertension, but its pathogenesis remains obscure. Genome‐wide association studies identified TRIM47 at the 17q25 locus as a top genetic risk factor for WMH formation. TRIM family class of E3 ubiquitin ligase pivotal functions in autophagy, which critical brain endothelial cell (ECs) remodeling during hypertension. We hypothesize that regulates autophagy loss‐of‐function disturbs...

Early-onset forms of familial Alzheimer's disease (FAD) are usually caused by mutations in three known genes: the amyloid precursor protein (APP), and two presenilin genes (PSEN1 PSEN2). APP is a single-transmembrane whose normal biological function largely unknown. The congruence FAD genetics presence plaque pathology has focused attention on proteolytic fragment Aβ, even while remains unexplored. To fill this gap our understanding, have studied axon initial segment (AIS), specialized...