Frankfurt am Main, Germany

Goethe University Frankfurt
Frankfurt am Main, Germany

The Goethe University Frankfurt is a university which was founded in 1914 as a Citizens' University, which means that, while it was a State university of Prussia, it had been founded and financed by the wealthy and active liberal citizenry of Frankfurt am Main, a unique feature in German university history. It was named in 1932 after one of the most famous natives of Frankfurt, the poet and writer Johann Wolfgang von Goethe. Today, the university has 46,000 students, on 4 major campuses within the city.Several Nobel Prize winners have been affiliated with the university, such as Max von Laue. The university is also affiliated with 11 winners of the Gottfried Wilhelm Leibniz Prize. Wikipedia.

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Duvarci S.,Goethe University Frankfurt | Pare D.,Rutgers University
Neuron | Year: 2014

We review recent work on the role of intrinsic amygdala networks in the regulation of classically conditioned defensive behaviors, commonly known as conditioned fear. These new developments highlight how conditioned fear depends on far more complex networks than initially envisioned. Indeed, multiple parallel inhibitory and excitatory circuits are differentially recruited during the expression versus extinction of conditioned fear. Moreover, shifts between expression and extinction circuits involve coordinated interactions with different regions of the medial prefrontal cortex. However, key areas of uncertainty remain, particularly with respect to the connectivity of the different cell types. Filling these gaps in our knowledge is important because much evidence indicates that human anxiety disorders results from an abnormal regulation of the networks supporting fear learning. Duvarci and Pare review recent work on the role of intrinsic amygdala networks in regulating conditioned fear, revealing that it depends on multiple parallel inhibitory and excitatory circuits that are differentially recruited during the expression versus extinction of conditioned fear. © 2014 Elsevier Inc.

Dikic I.,Goethe University Frankfurt
Annual Review of Biochemistry | Year: 2017

Autophagy and the ubiquitin-proteasome system are the two major quality control pathways responsible for cellular homeostasis. As such, they provide protection against age-associated changes and a plethora of human diseases. Ubiquitination is utilized as a degradation signal by both systems, albeit in different ways, to mark cargoes for proteasomal and lysosomal degradation. Both systems intersect and communicate at multiple points to coordinate their actions in proteostasis and organelle homeostasis. This review summarizes molecular details of how proteasome and autophagy pathways are functionally interconnected in cells and indicates common principles and nodes of communication that can be therapeutically exploited. © 2017 by Annual Reviews.

Kreuter J.,Goethe University Frankfurt
Advanced Drug Delivery Reviews | Year: 2012

The blood-brain barrier (BBB) represents an insurmountable obstacle for a large number of drugs, including antibiotics, antineoplastic agents, and a variety of central nervous system (CNS)-active drugs, especially neuropeptides. One of the possibilities to overcome this barrier is a drug delivery to the brain using nanoparticles. Drugs that have successfully been transported into the brain using this carrier include the hexapeptide dalargin, the dipeptide Kyotorphin, loperamide, tubocurarine, the NMDA receptor antagonist MRZ 2/576, and doxorubicin. The nanoparticles may be especially helpful for the treatment of the disseminated and very aggressive brain tumors. Intravenously injected doxorubicin-loaded polysorbate 80-coated nanoparticles were able to lead to a 40% cure in rats with intracranially transplanted glioblastomas 101/8. The mechanism of the nanoparticle-mediated transport of the drugs across the blood-brain barrier at present is not fully elucidated. The most likely mechanism is endocytosis by the endothelial cells lining the brain blood capillaries. Nanoparticle-mediated drug transport to the brain depends on the overcoating of the particles with polysorbates, especially polysorbate 80. Overcoating with these materials seems to lead to the adsorption of apolipoprotein E from blood plasma onto the nanoparticle surface. The particles then seem to mimic low density lipoprotein (LDL) particles and could interact with the LDL receptor leading to their uptake by the endothelial cells. After this the drug may be released in these cells and diffuse into the brain interior or the particles may be transcytosed. Other processes such as tight junction modulation or P-glycoprotein (Pgp) inhibition also may occur. Moreover, these mechanisms may run in parallel or may be cooperative thus enabling a drug delivery to the brain. © 2012 Elsevier B.V.

Laufs H.,Goethe University Frankfurt
NeuroImage | Year: 2012

In this personalized review, the history of EEG recorded simultaneously with functional MRI (EEG-fMRI) is summarized. A brief overview is given of the hardware development followed by a discussion of EEG-fMRI applications. The technique's development was clinically motivated in the context of epilepsy. Accordingly, the evolution of studies trying to identify with EEG-fMRI the origin of individual epileptiform discharges up to those revealing general mechanisms of epilepsy syndromes is sketched. In epilepsy centers experienced with the methodology, EEG-fMRI has found its place in the presurgical evaluation of patients. In cognitive neuroscience, the multimodal technique has significantly contributed to the understanding of phenomena of the resting state and neuronal oscillations. While most of the studies discussed relate EEG to fMRI by means of prediction, the development of forward models facilitating the symmetrical 'fusion' of EEG and fMRI data is the subject of current neuro-computational research. Recently, intracranial EEG has been safely recorded during (functional) MRI broadly extending the perspectives for epilepsy and research into neurovascular coupling. EEG-fMRI has evolved into a mature, generally accessible and in principle easily applicable technique, which is a great achievement. Because this at the same time bears the risk of unreflected use, EEG-fMRI safety issues are also highlighted. © 2012 Elsevier Inc.

Roeper J.,Goethe University Frankfurt
Trends in Neurosciences | Year: 2013

Midbrain dopamine (DA) neurons are essential for controlling key functions of the brain, such as voluntary movement, reward processing, and working memory. The largest populations of midbrain DA neurons are localized in two neighboring nuclei, the substantia nigra (SN) and the ventral tegmental area (VTA). Regardless of their different axonal projections to subcortical and cortical targets, midbrain DA neurons have traditionally been regarded as a relatively homogeneous group of neurons, with a stereotypical set of intrinsic electrophysiological properties and in vivo pattern of activity. In this review, I highlight recent data supporting an unexpected degree of diversity among these midbrain DA neurons in the mammalian brain, ranging from their developmental lineages and different synaptic connectivity to their electrophysiological properties and behavioral functions. © 2013 Elsevier Ltd.

Offermanns S.,Max Planck Institute for Heart and Lung Research | Offermanns S.,Goethe University Frankfurt
Annual Review of Pharmacology and Toxicology | Year: 2014

Saturated and unsaturated free fatty acids (FFAs), as well as hydroxy carboxylic acids (HCAs) such as lactate and ketone bodies, are carriers of metabolic energy, precursors of biological mediators, and components of biological structures. However, they are also able to exert cellular effects through G protein-coupled receptors named FFA1-FFA4 and HCA1-HCA3. Work during the past decade has shown that these receptors are widely expressed in the human body and regulate the metabolic, endocrine, immune and other systems to maintain homeostasis under changing dietary conditions. The development of genetic mouse models and the generation of synthetic ligands of individual FFA and HCA receptors have been instrumental in identifying cellular and biological functions of these receptors. These studies have produced strong evidence that several FFA and HCA receptors can be targets for the prevention and treatment of various diseases, including type 2 diabetes mellitus, obesity, and inflammation. © 2014 by Annual Reviews.

Strebhardt K.,Goethe University Frankfurt
Nature Reviews Drug Discovery | Year: 2010

The polo-like kinase 1 (PLK1) acts in concert with cyclin-dependent kinase 1-cyclin B1 and Aurora kinases to orchestrate a wide range of critical cell cycle events. Because PLK1 has been preclinically validated as a cancer target, small-molecule inhibitors of PLK1 have become attractive candidates for anticancer drug development. Although the roles of the closely related PLK2, PLK3 and PLK4 in cancer are less well understood, there is evidence showing that PLK2 and PLK3 act as tumour suppressors through their functions in the p53 signalling network, which guards the cell against various stress signals. In this article, recent insights into the biology of PLKs will be reviewed, with an emphasis on their role in malignant transformation, and progress in the development of small-molecule PLK1 inhibitors will be examined. © 2010 Macmillan Publishers Limited. All rights reserved.

Kaschube M.,Goethe University Frankfurt
Current Opinion in Neurobiology | Year: 2014

Theoretical neuroscientists have long been intrigued by the spatial patterns of neuronal selectivities observed in the visual cortices of many mammals, including primates. While theoretical studies have contributed significantly to our understanding of how the brain learns to see, recent experimental discoveries of the spatial irregularity of visual response properties in the rodent visual cortex have prompted new questions about the origin and functional significance of cortical maps. Characterizing the marked differences of cortical design principles among species and comparing them may provide us with a deeper understanding of primate and non-primate vision. © 2013 Elsevier Ltd.

Kreuter J.,Goethe University Frankfurt
Advanced Drug Delivery Reviews | Year: 2014

Nanoparticles enable the delivery of a great variety of drugs including anticancer drugs, analgesics, anti-Alzheimer's drugs, cardiovascular drugs, protease inhibitors, and several macromolecules into the brain after intravenous injection of animals. The mechanism of the nanoparticle-mediated drug transport across the BBB appears to be receptor-mediated endocytosis followed by transcytosis into the brain or by drug release within the endothelial cells. Modification of the nanoparticle surface with covalently attached targeting ligands or by coating with certain surfactants that lead to the adsorption of specific plasma proteins after injection is necessary for this receptor-mediated uptake. A very critical and important requirement for nanoparticulate brain delivery is that the employed nanoparticles are biocompatible and, moreover, rapidly biodegradable, i.e. over a time frame of a few days. In addition to enabling drug delivery to the brain, nanoparticles, as with doxorubicin, may importantly reduce the drug's toxicity and adverse effects due to an alteration of the body distribution. Because of the possibility to treat severe CNS diseases such as brain tumours and to even transport proteins and other macromolecules across the blood-brain barrier, this technology holds great promise for a non-invasive therapy of these diseases. © 2013 Elsevier B.V.

Over the last 20 years, it has become clear that cytochrome P450 (P450) enzymes generate a spectrum of bioactive lipid mediators from endogenous substrates. However, studies focused on the determining biologic activity of the P450 system have focused largely on the metabolites generated by one substrate (i.e., arachidonic acid). However, epoxides and diols derived from other endogenous substrates, such as linoleic acid, eicosapentaenoic acid, and docosahexaenoic acid, may be generated in higher concentrations and may potentially be of more physiologic relevance. Recent studies that used a combination of phenotyping and lipid array analyses revealed that rather than being inactive products, fatty acid diols play important roles in a number of biologic processes including inflammation, angiogenesis, and metabolic regulation. Moreover, inhibitors of the soluble epoxide hydrolase that increase epoxide but decrease diol levels have potential for the treatment of the metabolic syndrome. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

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