0000000000015931

AUTHOR

Mario Kreutzfeldt

0000-0003-0335-2733

showing 2 related works from this author

The K63 deubiquitinase CYLD modulates autism-like behaviors and hippocampal plasticity by regulating autophagy and mTOR signaling.

2021

Nondegradative ubiquitin chains attached to specific targets via Lysine 63 (K63) residues have emerged to play a fundamental role in synaptic function. The K63-specific deubiquitinase CYLD has been widely studied in immune cells and lately also in neurons. To better understand if CYLD plays a role in brain and synapse homeostasis, we analyzed the behavioral profile of CYLD-deficient mice. We found that the loss of CYLD results in major autism-like phenotypes including impaired social communication, increased repetitive behavior, and cognitive dysfunction. Furthermore, the absence of CYLD leads to a reduction in hippocampal network excitability, long-term potentiation, and pyramidal neuron s…

MaleAutism Spectrum DisorderNerve Tissue ProteinsHippocampal formationHippocampusDeubiquitinating enzymeSynapseMiceUbiquitinAutophagyAnimalsAutistic DisorderMechanistic target of rapamycinPI3K/AKT/mTOR pathwayNeuronsMultidisciplinarybiologyUbiquitinLysineTOR Serine-Threonine KinasesAutophagyMicrofilament ProteinsUbiquitinationLong-term potentiationBiological SciencesDeubiquitinating Enzyme CYLDMice Inbred C57BLSynapsesbiology.proteinFemaleNeuroscienceSignal TransductionProceedings of the National Academy of Sciences of the United States of America
researchProduct

Interferon-γ-Driven iNOS: A Molecular Pathway to Terminal Shock in Arenavirus Hemorrhagic Fever

2017

Arenaviruses such as Lassa virus (LASV) cause hemorrhagic fever. Terminal shock is associated with a systemic cytokine storm, but the mechanisms are ill defined. Here we used HLA-A2-expressing mice infected with a monkey-pathogenic strain of lymphocytic choriomeningitis virus (LCMV-WE), a close relative of LASV, to investigate the pathophysiology of arenavirus hemorrhagic fever (AHF). AHF manifested as pleural effusions, edematous skin swelling, and serum albumin loss, culminating in hypovolemic shock. A characteristic cytokine storm included numerous pro-inflammatory cytokines and nitric oxide (NO) metabolites. Edema formation and terminal shock were abrogated in mice lacking inducible nit…

0301 basic medicineMaleHemorrhagic Fevers ViralNitric Oxide Synthase Type IIBiologyLymphocytic Choriomeningitisddc:616.07Lymphocytic choriomeningitismedicine.disease_causeNitric OxideMicrobiologyViral hemorrhagic fever03 medical and health sciencesInterferon-gammaMice0302 clinical medicineVirologymedicineAnimalsHumansLymphocytic choriomeningitis virusLassa feverArenavirusddc:617medicine.diseasebiology.organism_classification3. Good healthNitric oxide synthaseMice Inbred C57BLDisease Models Animal030104 developmental biologyLassa virus030220 oncology & carcinogenesisShock (circulatory)Immunologybiology.proteinParasitologyFemalemedicine.symptomCytokine storm
researchProduct