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Wardlaw J.M.,University of Edinburgh | Smith C.,University of Edinburgh | Dichgans M.,Ludwig Maximilians University of Munich | Dichgans M.,German Center for Neurodegenerative Diseases | Dichgans M.,Synergy Systems
The Lancet Neurology | Year: 2013

The term cerebral small vessel disease (SVD) describes a range of neuroimaging, pathological, and associated clinical features. Clinical features range from none, to discrete focal neurological symptoms (eg, stroke), to insidious global neurological dysfunction and dementia. The burden on public health is substantial. The pathogenesis of SVD is largely unknown. Although the pathological processes leading to the arteriolar disease are associated with vascular risk factors and are believed to result from an intrinsic cerebral arteriolar occlusive disease, little is known about how these processes result in brain disease, how SVD lesions contribute to neurological or cognitive symptoms, and the association with risk factors. Pathology often shows end-stage disease, which makes identification of the earliest stages difficult. Neuroimaging provides considerable insights; although the small vessels are not easily seen themselves, the effects of their malfunction on the brain can be tracked with detailed brain imaging. We discuss potential mechanisms, detectable with neuroimaging, that might better fit the available evidence and provide testable hypotheses for future study. © 2013 Elsevier Ltd. Source

Hemmer B.,TU Munich | Hemmer B.,Synergy Systems | Kerschensteiner M.,Ludwig Maximilians University of Munich | Kerschensteiner M.,Synergy Systems | And 2 more authors.
The Lancet Neurology | Year: 2015

Multiple sclerosis is a chronic disease of the CNS that leads to substantial disability in most patients. The early phase is characterised by relapses and the later phase by progressive disability. Results from immunological, genetic, and histopathological studies and treatment trials have shown that the immune system plays a key part in the disease course. Findings from animal models and immunological studies of patients with multiple sclerosis suggest a change in the involvement of the immune system during disease initiation and progression. These findings suggest that a peripheral immune response targeting the CNS drives the disease process during the early phase, whereas immune reactions within the CNS dominate the progressive phase. These concepts for the differential involvement of immune responses in the early and progressive phase of this disease have important implications for future research in the pathogenesis and treatment of multiple sclerosis. © 2015 Elsevier Ltd. Source

Banzhaf-Strathmann J.,German Center for Neurodegenerative Diseases | Edbauer D.,German Center for Neurodegenerative Diseases | Edbauer D.,Ludwig Maximilians University of Munich | Edbauer D.,Synergy Systems
Cell Communication and Signaling | Year: 2014

MicroRNAs (miRNAs) are a class of non-coding RNAs that post- transcriptionally silence target mRNAs. Dysregulation of miRNAs is a frequent event in several diseases, including cancer. One miRNA that has gained special interest in the field of cancer research is miRNA-125b (miR-125b). MiR-125b is a ubiquitously expressed miRNA that is aberrantly expressed in a great variety of tumors. In some tumor types, e.g. colon cancer and hematopoietic tumors, miR-125b is upregulated and displays oncogenic potential, as it induces cell growth and proliferation, while blocking the apoptotic machinery. In contrast, in other tumor entities, e.g. mammary tumors and hepatocellular carcinoma, miR-125b is heavily downregulated. This downregulation is accompanied by de-repression of cellular proliferation and anti-apoptotic programs, contributing to malignant transformation. The reasons for these opposing roles are poorly understood. We summarize the current knowledge of miR-125b and its relevant targets in different tumor types and offer several hypotheses for the opposing roles of miR-125b: miR-125b targets multiple mRNAs, which have diverse functions in individual tissues. These target mRNAs are tissue and tumor specifically expressed, suggesting that misregulation by miR-125b depends on the levels of target gene expression. Moreover, we provide several examples that miR-125b upregulation dictates oncogenic characteristics, while downregulation of miR-125b corresponds to the loss of tumor suppressive functions. Thus, in different tumor entities increased or decreased miR-125b expression may contribute to carcinogenesis. © 2014 Banzhaf-Strathmann and Edbauer; licensee BioMed Central Ltd. Source

Falcone G.J.,Massachusetts General Hospital | Falcone G.J.,Cambridge Broad Institute | Falcone G.J.,Harvard University | Malik R.,Ludwig Maximilians University of Munich | And 4 more authors.
The Lancet Neurology | Year: 2014

Driven by innovative technologies, novel analytical methods, and collaborations unimaginable not long ago, our understanding of the role of genetic variation in stroke has advanced substantially in recent years. However, a vast amount of data have accumulated quickly, and increasingly complex methodologies used in studies make keeping up to date on relevant findings difficult. In addition to well known, highly penetrant rare mutations that cause mendelian disorders related to stroke, several common genetic variants have been associated with common stroke subtypes, some of which also affect disease severity and clinical outcome. Furthermore, common genetic variations in biological pathways that have an important role in the pathophysiology of cerebrovascular diseases-such as blood pressure and oxidative phosphorylation-have been implicated in stroke. Clinical and translational applications of these and future discoveries in stroke genetics include identification of novel targets for treatment and development of personalised approaches to stroke prevention and management. © 2014 Elsevier Ltd. Source

Klein R.,Max Planck Institute of Neurobiology | Klein R.,Synergy Systems | Kania A.,Institute Of Recherches Cliniques Of Montreal Ircm | Kania A.,University of Montreal | Kania A.,McGill University
Current Opinion in Neurobiology | Year: 2014

Ephrin ligands and their Eph receptors hold our attention since their link to axon guidance almost twenty years ago. Since then, they have been shown to be critical for short distance cell-cell interactions in the nervous system. The interest in their function has not abated, leading to ever-more sophisticated studies generating as many surprising answers about their function as new questions. We discuss recent insights into their functions in the developing nervous system, including neuronal progenitor sorting, stochastic cell migration, guidance of neuronal growth cones, topographic map formation, as well as synaptic plasticity. © 2014 Elsevier Ltd. Source

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