Time-dependent olfactory proteomics in Tg2576 mice
ABSTRACT: Olfaction is often deregulated in Alzheimer´s disease (AD) patients, being also impaired in transgenic Tg2576 AD mouse model, which overexpress the Swedish mutated form of human amyloid precursor protein (APP). However, little is known about the molecular mechanisms that accompany the neurodegeneration of olfactory structures in Tg2576 mice. For that, we have applied proteome-wide approaches to probe molecular disturbances in the olfactory bulb (OB) dissected from Tg2576 mice respect to age matched wild-type littermates (2 and 6 months of age).
The olfactory bulb (OB) is the first processing station in the olfactory pathway. Despite smell impairment, which is considered an early event in Alzheimer's disease (AD), little is known about the initial molecular disturbances that accompany the AD development at olfactory level. We have interrogated the time-dependent OB molecular landscape in Tg2576 AD mice prior to the appearance of neuropathological amyloid plaques (2-, and 6-month-old), using combinatorial omics analysis. The metabolic mo ...[more]
Project description:Olfaction is often deregulated in Alzheimer´s disease (AD) patients, being also impaired in transgenic Tg2576 AD mouse model, which overexpress the Swedish mutated form of human amyloid precursor protein (APP). However, little is known about the molecular mechanisms that accompany the neurodegeneration of olfactory structures in Tg2576 mice. For that, we have applied proteome- and transcriptome-wide approaches to probe molecular disturbances in the olfactory bulb (OB) dissected from aged Tg2576 mice (18 months of age) respect to age matched wild-type (WT) littermates
Project description:Glioblastoma multiforme (GBM) is the most common and aggressive type of malignant glioma. Oncolytic adenoviruses are being modified to exploit the aberrant expression of proteins in tumor cells to enhance tumor tropism and glioma-selective replication. E1A mutant adenovirus Delta-24-RGD has shown favorable toxicity profile and remarkable efficacy in a first-in-human phase I clinical trial. However, the comprehensive modulation of glioma metabolism in response to Delta-24-RGD infection is poorly understood. Integrating mass spectrometry based-quantitative proteomics, physical and functional interaction data, and biochemical approaches, we conducted a cell-wide study of cytosolic, nuclear, and secreted glioma proteomes throughout the early time course of Delta-24-RGD infection.
Project description:In order to analyse the 293T-MDSCs proteome in a large-scale format, we used a fractionation approach which combines peptide chromatographic fractionation strategies coupled to mass spectrometry.
Project description:In order to analyse the B16-MDSCs proteome in a large-scale format, we used a multi-dimensional fractionation approach which combines peptide chromatographic fractionation strategies coupled to mass spectrometry.
Project description:Olfactory dysfunction is among the earliest features of Alzheimer´s disease (AD). Although neuropathological abnormalities have been detected in the olfactory bulb (OB), little is known about its dynamic biology. Here, OB- proteome analysis was performed across different AD stages using a label-free approach.
Project description:Olfactory dysfunction is one of the earliest features in Lewy-type alpha-synucleinopathies (LTS) such as Parkinson´s disease (PD). However, the underlying molecular mechanisms associated to smell impairment is poorly understood. To reveal the missing links in the biochemical understanding of olfactory dysfunction in PD, we have applied mass spectrometry-based proteomics in postmortem olfactory bulbs (OBs) dissected from parkinsonian subjects with different LTS staging respect to elderly controls (n= 24, mean age 79 years).
Project description:To investigate how TBP-2/Txnip regulates insulin sensitivity in the skeletal muscle, we performed microarray analyses. The gene expression in the skeletal muscle from WT, TBP-2-/-, ob/ob, ob/ob TBP-2-/- at 10 weeks age were performed.
Project description:Here we used double-transgenic amyloid precursor protein/presenilin 1 (APPswe/PS1dE9) mice and label-free quantitative proteomics to analyze potential early pathological effects on the olfactory bulb (OB) during AD progression.
Project description:We examined the effect of oral TUDCA treatment on hepatic steatosis and associated changes in hepatic gene expression in ob/ob mice. We administered TUDCA to ob/ob mice at a dose of 500 mg/kg twice a day by gastric gavage for 3 weeks. Body weight, glucose homeostasis, endoplasmic reticulum (ER) stress, and hepatic gene expression were examined in comparison with control ob/ob mice and normal littermate C57BL/6J mice.