Bonn, Germany

The German Center for Neurodegenerative Diseases aims to develop new preventive and therapeutic approaches for neurodegenerative diseases. To accomplish this the DZNE follows a translational approach. This means that fundamental research is closely related to clinical research, population studies and health care research. In total there are nine sites all over Germany: Berlin, Bonn, Dresden, Göttingen, Magdeburg, Munich, Rostock / Greifswald, Tübingen and Witten. At each site the DZNE works closely with universities, university hospitals and other partners.The DZNE receives 90 percent of its funding from the Federal Ministry of Education and Research and 10 percent from the respective federal states containing DZNE sites. Wikipedia.


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Zempel H.,German Center for Neurodegenerative Diseases | Mandelkow E.,German Center for Neurodegenerative Diseases | Mandelkow E.,Max Planck Institute for Neurological Research
Trends in Neurosciences | Year: 2014

Tau is a microtubule-associated-protein that is sorted into neuronal axons in physiological conditions. In Alzheimer disease (AD) and other tauopathies, Tau sorting mechanisms fail and Tau becomes missorted into the somatodendritic compartment. In AD, aberrant amyloid-β (Aβ) production might trigger Tau missorting. The physiological axonal sorting of Tau depends on the developmental stage of the neuron, the phosphorylation state of Tau and the microtubule cytoskeleton. Disease-associated missorting of Tau is connected to increased phosphorylation and aggregation of Tau, and impaired microtubule interactions. Disease-causing mechanisms involve impaired transport, aberrant kinase activation, non-physiological interactions of Tau, and prion-like spreading. In this review we focus on the physiological and pathological (mis)sorting of Tau, the underlying mechanisms, and effects in disease. © 2014 Elsevier Ltd.


Fischer A.,University of Gottingen | Fischer A.,German Center for Neurodegenerative Diseases
EMBO Journal | Year: 2014

Recent data support the view that epigenetic processes play a role in memory consolidation and help to transmit acquired memories even across generations in a Lamarckian manner. Drugs that target the epigenetic machinery were found to enhance memory function in rodents and ameliorate disease phenotypes in models for brain diseases such as Alzheimer's disease, Chorea Huntington, Depression or Schizophrenia. In this review, I will give an overview on the current knowledge of epigenetic processes in memory function and brain disease with a focus on Morbus Alzheimer as the most common neurodegenerative disease. I will address the question whether an epigenetic therapy could indeed be a suitable therapeutic avenue to treat brain diseases and discuss the necessary steps that should help to take neuroepigenetic research to the next level. As part of our review series on Molecular Memory, Andre Fischer discusses epigenetic processes leading to memory formation and transgenerational inheritance under physiological and pathological conditions such as Alzheimer's disease. © 2014 The Author. Published under the terms of the CC BY NC ND license.


Eisenberg D.,Howard Hughes Medical Institute | Jucker M.,University of Tübingen | Jucker M.,German Center for Neurodegenerative Diseases
Cell | Year: 2012

Amyloid fibers and oligomers are associated with a great variety of human diseases including Alzheimer's disease and the prion conditions. Here we attempt to connect recent discoveries on the molecular properties of proteins in the amyloid state with observations about pathological tissues and disease states. We summarize studies of structure and nucleation of amyloid and relate these to observations on amyloid polymorphism, prion strains, coaggregation of pathogenic proteins in tissues, and mechanisms of toxicity and transmissibility. Molecular studies have also led to numerous strategies for biological and chemical interventions against amyloid diseases. © 2012 Elsevier Inc.


Ulusoy A.,German Center for Neurodegenerative Diseases
Molecular neurobiology | Year: 2013

The discovery of α-synuclein has had profound implications concerning our understanding of Parkinson's disease (PD) and other neurodegenerative disorders characterized by α-synuclein accumulation. In fact, as compared with pre-α-synuclein times, a "new" PD can now be described as a whole-body disease in which a progressive spreading of α-synuclein pathology underlies a wide spectrum of motor as well as nonmotor clinical manifestations. Not only is α-synuclein accumulation a pathological hallmark of human α-synucleinopathies but increased protein levels are sufficient to trigger neurodegenerative processes. α-Synuclein elevations could also be a mechanism by which disease risk factors (e.g., aging) increase neuronal vulnerability to degeneration. An important corollary to the role of enhanced α-synuclein in PD pathogenesis is the possibility of developing α-synuclein-based biomarkers and new therapeutics aimed at suppressing α-synuclein expression. The use of in vitro and in vivo experimental models, including transgenic mice overexpressing α-synuclein and animals with viral vector-mediated α-synuclein transduction, has helped clarify pathogenetic mechanisms and therapeutic strategies involving α-synuclein. These models are not devoid of significant limitations, however. Therefore, further pursuit of new clues on the cause and treatment of PD in this post-α-synuclein era would benefit substantially from the development of improved research paradigms of α-synuclein elevation.


Kempermann G.,Center for Regenerative Therapies Dresden | Kempermann G.,German Center for Neurodegenerative Diseases
Cell | Year: 2011

The reports by Bonaguidi et al. (in this issue of Cell) and Encinas et al. (in Cell Stem Cell) come to differing conclusions about whether and how the proliferation of radial glia-like stem cells of the adult hippocampus impacts their long-term potential for neurogenesis. © 2011 Elsevier Inc.


Jackson W.S.,German Center for Neurodegenerative Diseases
DMM Disease Models and Mechanisms | Year: 2014

The mechanisms underlying the selective targeting of specific brain regions by different neurodegenerative diseases is one of the most intriguing mysteries in medicine. For example, it is known that Alzheimer's disease primarily affects parts of the brain that play a role in memory, whereas Parkinson's disease predominantly affects parts of the brain that are involved in body movement. However, the reasons that other brain regions remain unaffected in these diseases are unknown. A better understanding of the phenomenon of selective vulnerability is required for the development of targeted therapeutic approaches that specifically protect affected neurons, thereby altering the disease course and preventing its progression. Prion diseases are a fascinating group of neurodegenerative diseases because they exhibit a wide phenotypic spectrum caused by different sequence perturbations in a single protein. The possible ways that mutations affecting this protein can cause several distinct neurodegenerative diseases are explored in this Review to highlight the complexity underlying selective vulnerability. The premise of this article is that selective vulnerability is determined by the interaction of specific protein conformers and region-specific microenvironments harboring unique combinations of subcellular components such as metals, chaperones and protein translation machinery. Given the abundance of potential contributory factors in the neurodegenerative process, a better understanding of how these factors interact will provide invaluable insight into disease mechanisms to guide therapeutic discovery. © 2014. Published by The Company of Biologists Ltd.


Kempermann G.,German Center for Neurodegenerative Diseases
Cold Spring Harbor Perspectives in Biology | Year: 2015

Age and activity might be considered the two antagonistic key regulators of adult neurogenesis. Adult neurogenesis decreases with age but remains present, albeit at a very low level, even in the oldest individuals. Activity, be it physical or cognitive, increases adult neurogenesis and thereby seems to counteract age effects. It is, thus, proposed that activity- dependent regulation of adult neurogenesis might contribute to some sort of “neural reserve,” the brain’s ability to compensate functional loss associated with aging or neurodegeneration. Activity can have nonspecific and specific effects on adult neurogenesis. Mechanistically, nonspecific stimuli that largely affect precursor cell stages might be related by the local microenvironment, whereas more specific, survival-promoting effects take place at later stages of neuronal development and require the synaptic integration of the new cell and its particular synaptic plasticity. © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.


Berg D.,German Center for Neurodegenerative Diseases
Parkinsonism and Related Disorders | Year: 2012

The increasing knowledge about an ongoing neurodegenerative process long before the diagnosis of Parkinson's disease (PD) can be made according to the current diagnostic criteria urges the need for an earlier diagnosis with the final aim of neuromodulatory and neuroprotective therapies. A number of risk, pre-motor and early motor markers are being discussed as potential markers to identify individuals who will develop the full picture of clinical PD. In Europe, studies like the PRIPS study (Prospective validation of RIsk factors for the development of Parkinson Syndromes) are performed to determine the sensitivity and predictive value of markers. In enriched risk cohorts like cohorts of individuals with RBD (Rem sleep Behaviour Disorder) or the TREND study (T ̈ ubinger evaluation of Risk factors for Early detection of NeuroDegeneration) specificity of markers is determined and further markers are evaluated. Moreover, progression of markers in the pre-motor period is being evaluated in these studies; for example, in the PMPP study (Progression Markers in the suspected Pre-motor Phase) assessments are performed at shorter time intervals. Establishing sensitivity, specificity, predictive value and progression of markers in yet healthy individuals are hoped to lay the basis for future interventional trials before the onset of motor-PD. © 2011 Elsevier Ltd.


Kempermann G.,German Center for Neurodegenerative Diseases
Cell | Year: 2014

In the adult brain, new neurons are produced in two "canonical" regions: the hippocampus and the olfactory bulb. Ernst et al. now show that, unlike other species, humans also display robust neurogenesis in the striatum, an unexpected finding with important physiological, pathological, and evolutionary implications. © 2014 Elsevier Inc.


Tedeschi A.,German Center for Neurodegenerative Diseases | Bradke F.,German Center for Neurodegenerative Diseases
EMBO Reports | Year: 2013

Dual leucine zipper kinase (DLK), a mitogen-activated protein kinase kinase kinase, controls axon growth, apoptosis and neuron degeneration during neural development, as well as neurodegeneration after various insults to the adult nervous system. Interestingly, recent studies have also highlighted a role of DLK in promoting axon regeneration in diverse model systems. Invertebrates and vertebrates, cold- and warm-blooded animals, as well as central and peripheral mammalian nervous systems all differ in their ability to regenerate injured axons. Here, we discuss how DLK-dependent signalling regulates apparently contradictory functions during neural development and regeneration in different species. In addition, we outline strategies to fine-tune DLK function, either alone or together with other approaches, to promote axon regeneration in the adult mammalian central nervous system. © 2013 European Molecular Biology Organization.

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