Search results for "Pathway"

Notch and TLR signaling coordinate monocyte cell fate and inflammation

2020

AbstractConventional Ly6Chi monocytes have developmental plasticity for a spectrum of differentiated phagocytes. Here we show, using conditional deletion strategies in a mouse model of Toll-like receptor (TLR) 7-induced inflammation, that the spectrum of developmental cell fates of Ly6Chi monocytes, and the resultant inflammation, is coordinately regulated by TLR and Notch signaling. Cell-intrinsic Notch2 and TLR7-Myd88 pathways independently and synergistically promote Ly6Clo patrolling monocyte development from Ly6Chi monocytes under inflammatory conditions, while impairment in either signaling axis impairs Ly6Clo monocyte development. At the same time, TLR7 stimulation in the absence of …

Data set of interactomes and metabolic pathways of proteins differentially expressed in brains with Alzheimer׳s disease

2016

Alzheimer's disease is one of the main causes of dementia in the elderly and its frequency is on the rise worldwide. It is considered the result of complex interactions between genetic and environmental factors, being many of them unknown. Therefore, there is a dire necessity for the identification of novel molecular players for the understanding of this disease. In this data article we determined the protein expression profiles of whole protein extracts from cortex regions of brains from patients with Alzheimer's disease in comparison to a normal brain. We identified 721 iTRAQ-labeled polypeptides with more than 95% in confidence. We analyzed all proteins that changed in their expression l…

Identification of Cysteine Ubiquitylation Sites on the Sec23A Protein of the COPII Complex Required for Vesicle Formation from the ER

2017

Background COPII is a multiprotein complex that surrounds carrier vesicles budding from the Endoplasmic Reticulum and allows the recruitment of secretory proteins. The Sec23a protein plays a crucial role in the regulation of the dynamics of COPII formation ensuring the proper function of the secretory pathway. Objective Since few evidences suggest that ubiquitylation could have a role in the COPII regulation, the present study was aimed to establish whether the Sec23a component of the vesicular envelope COPII could be ubiquitylated. Method Sec23a ubiquitylation was revealed by co-immunoprecipitation experiments. Recombinant Sec23a was gel-purified and analyzed by mass spectrometry subjected…

2020

Sclerosing spindle cell rhabdomyosarcoma (SSRMS) is a rare rhabdomyosarcomas (RMS) subtype. Especially cases bearing a myogenic differentiation 1 (MYOD1) mutation are characterized by a high recurrence and metastasis rate, often leading to a fatal outcome. SSRMS cell lines are valuable in vitro models for studying disease mechanisms and for the preclinical evaluation of new therapeutic approaches. In this study, a cell line established from a primary SSRMS tumor of a 24-year-old female after multimodal chemotherapeutic pretreatment has been characterized in detail, including immunohistochemistry, growth characteristics, cytogenetic analysis, mutation analysis, evaluation of stem cell marker…

Nrf2 expression driven by Foxp3 specific deletion of Keap1 results in loss of immune tolerance in mice

2020

European journal of immunology 50(4), 515-524 (2020). doi:10.1002/eji.201948285

Genetic regulation and function of epidermal growth factor receptor signalling in patterning of the embryonicDrosophilabrain

2016

The specification of distinct neural cell types in central nervous system development crucially depends on positional cues conferred to neural stem cells in the neuroectoderm. Here, we investigate the regulation and function of the epidermal growth factor receptor (EGFR) signalling pathway in early development of theDrosophilabrain. We find that localized EGFR signalling in the brain neuroectoderm relies on a neuromere-specific deployment of activating (Spitz, Vein) and inhibiting (Argos) ligands. Activated EGFR controls the spatially restricted expression of all dorsoventral (DV) patterning genes in a gene- and neuromere-specific manner. Further, we reveal a novel role of DV genes—ventral …

TOX3 regulates neural progenitor identity

2016

The human genomic locus for the transcription factor TOX3 has been implicated in susceptibility to restless legs syndrome and breast cancer in genome-wide association studies, but the physiological role of TOX3 remains largely unknown. We found Tox3 to be predominantly expressed in the developing mouse brain with a peak at embryonic day E14 where it co-localizes with the neural stem and progenitor markers Nestin and Sox2 in radial glia of the ventricular zone and intermediate progenitors of the subventricular zone. Tox3 is also expressed in neural progenitor cells obtained from the ganglionic eminence of E15 mice that express Nestin, and it specifically binds the Nestin promoter in chromati…

Binge-like ethanol treatment in adolescence impairs autophagy and hinders synaptic maturation: Role of TLR4.

2018

Abstract Adolescence is a developmental period of brain maturation in which remodeling and changes in synaptic plasticity and neural connectivity take place in some brain regions. A different mechanism participates in adolescent brain maturation, including autophagy processes that play a role in synaptic development and plasticity. Alcohol is a neurotoxic compound whose abuse in adolescence causes TLR4 response activation by triggering neuroinflammation, neural damage and behavioral alterations. However, the potential participation of autophagy in long-term neurochemical and cognitive dysfunctions induced by binge ethanol drinking in adolescence is uncertain. We therefore evaluated whether …

Intrinsic volatility of synaptic connections — a challenge to the synaptic trace theory of memory

2017

According to the synaptic trace theory of memory, activity-induced changes in the pattern of synaptic connections underlie the storage of information for long periods. In this framework, the stability of memory critically depends on the stability of the underlying synaptic connections. Surprisingly however, synaptic connections in the living brain are highly volatile, which poses a fundamental challenge to the synaptic trace theory. Here we review recent experimental evidence that link the initial formation of a memory with changes in the pattern of connectivity, but also evidence that synaptic connections are considerably volatile even in the absence of learning. Then we consider different…

The Role of Anabolic Androgenic Steroids in Disruption of the Physiological Function in Discrete Areas of the Central Nervous System

2017

: Anabolic-androgenic steroids (AAS) abuse is often associated with a wide spectrum of adverse effects. These drugs are frequently abused by adolescents and athletes for esthetic purposes, as well as for improvement of their endurance and performances. In this literature review, we evaluated the correlation between AAS and anxiety or aggression. Two pathways are thought to be involved in AAS-induced behavioral disorders. Direct pathway via the amygdalo-fugal pathway, which connects the central nucleus of the amygdala to the brainstem, is involved in cognitive-emotive and homeostatic processes. The latter is modified by chronic AAS use, which subsequently leads to increased anxiety. Indirect…