Publications by authors named "Sebastian Höpfner"

5 Publications

  • Page 1 of 1

At a glance: the European patent with unitary effect.

Pharm Pat Anal 2016 Sep 17;5(5):295-300. Epub 2016 Aug 17.

Bird & Bird LLP, Maximiliansplatz 22, 80333 Munich, Germany.

Everything is almost ready for a new patent system to come into force in Europe. Its implementation will provide access to a unitary patent and a Unified Patent Court that can be used to centrally enforce and invalidate patents in the relevant member states. This system will provide several advantages and will create a more business-friendly Europe regarding intellectual property rights. However, also some risks are associated with the new system. This article will provide a general overview over this future system and highlight some strategic options that may be considered when assessing patent filing, enforcement and clearance strategies.
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http://dx.doi.org/10.4155/ppa-2016-0025DOI Listing
September 2016

Patent filing strategies for pharmaceuticals in Europe.

Pharm Pat Anal 2014 ;3(6):563-5

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http://dx.doi.org/10.4155/ppa.14.49DOI Listing
October 2015

Caenorhabditis elegans screen reveals role of PAR-5 in RAB-11-recycling endosome positioning and apicobasal cell polarity.

Nat Cell Biol 2012 May 27;14(7):666-76. Epub 2012 May 27.

Max Planck Institute of Molecular Cell Biology and Genetics, MPI-CBG, Pfotenhauerstrasse 108, 01307 Dresden, Germany.

Apically enriched Rab11-positive recycling endosomes (Rab11-REs) are important for establishing and maintaining epithelial polarity. Yet, little is known about the molecules controlling trafficking of Rab11-REs in an epithelium in vivo. Here, we report a genome-wide, image-based RNA interference screen for regulators of Rab11-RE positioning and transport of an apical membrane protein (PEPT-1) in C. elegans intestine. Among the 356 screen hits was the 14-3-3 and partitioning defective protein PAR-5, which we found to be specifically required for Rab11-RE positioning and apicobasal polarity maintenance. Depletion of PAR-5 induced abnormal clustering of Rab11-REs to ectopic sites at the basolateral cortex containing F-actin and other apical domain components. This phenotype required key regulators of F-actin dynamics and polarity, such as Rho GTPases (RHO-1 and the Rac1 orthologue CED-10) and apical PAR proteins. Our data suggest that PAR-5 acts as a regulatory hub for a polarity-maintaining network required for apicobasal asymmetry of F-actin and proper Rab11-RE positioning.
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http://dx.doi.org/10.1038/ncb2508DOI Listing
May 2012

Regulation of endosome dynamics by Rab5 and Huntingtin-HAP40 effector complex in physiological versus pathological conditions.

Methods Enzymol 2008 ;438:239-57

Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.

Vesicular transport of signaling molecules, specifically neurotrophins, in neurons is essential for their differentiation, survival, and plasticity. Neurotrophins such as neuron growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are internalized by receptor-mediated endocytosis at synaptic terminals and loaded into endosomes for microtubule-based transport along axons to the cell body where they exert their signaling function in the nucleus. The molecular mechanisms underlying this intracellular transport are not only relevant from a basic knowledge viewpoint, but have also important implications for neurodegenerative diseases. Defects in trafficking are increasingly implicated in the pathology of Huntington's disease (HD) and other neurodegenerative disorders. The small GTPases Rab5 and Rab7 play important roles in the endocytic trafficking of neurotrophins. We have recently identified Huntingtin (Htt) and Huntingtin associated protein of 40 kDa (HAP40) as a novel Rab5 effector complex that regulates endosome motility. In HD, we detected higher HAP40 protein levels compared with normal cells. Such increase causes an augmented recruitment of Htt onto Rab5-positive early endosomes that drastically reduces their motility by "switching" these organelles from microtubules to F-actin. These findings suggest a mechanism by which impaired Rab5-mediated trafficking of neurotrophic factors may be a key event of the pathogenetic process leading to neurodegeneration in HD. To dissect the mechanisms by which Htt, HAP40, and Rab5 function in early endosome interactions with the cytoskeleton, we developed assays to investigate endosome-cytoskeleton interactions that can be applied to normal and pathological conditions. We provide here detailed protocols for, first, an assay that measures binding of early endosomes to microtubules and F-actin. Second, we describe an improved protocol for a cell-free assay that recapitulates the motility of early endosomes along microtubules in vitro. These assays provide mechanistic insights into the dysfunction of endosome motility occurring in HD as well as other neurodegenerative disorders.
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http://dx.doi.org/10.1016/S0076-6879(07)38017-8DOI Listing
June 2008

A newly identified chromosomal microdeletion and an N-box mutation of the AChR epsilon gene cause a congenital myasthenic syndrome.

Brain 2002 May;125(Pt 5):1005-13

Genzentrum and Friedrich-Baur-Institut, Ludwig-Maximilians-University Munich, Germany.

Congenital myasthenic syndromes (CMSs) are frequently caused by mutations of the coding region of the acetylcholine receptor epsilon subunit (AChRepsilon) gene leading to a reduced expression of the acetylcholine receptor (AChR) at the postsynaptic membrane. Two recent observations have linked two different N-box mutations of the human AChRepsilon promoter to a clinical CMS phenotype. N-boxes are regulatory sequence elements of mammalian promoters that confer synapse-specific expression of several genes, including the AChR subunit genes. Here, we report on a novel point mutation (epsilon-154G-->A) in the N-box of the AChRepsilon promoter in a German CMS pedigree. Semiquantitative analysis of AChRepsilon mRNA levels in the patient's muscle indicated significantly impaired AChRepsilon expression. We provide additional evidence of a pathogenic role for this mutation using the mutated promoter (epsilon-154G-->A) driving a heterologous gene (luciferase) in rat skeletal muscle. We show that agrin-induced gene expression is significantly reduced by the N-box mutant (mt) compared with the wild-type (wt) promoter. Refined haplotype analysis and direct sequencing revealed maternal inheritance of the mutant AChRepsilon promoter (epsilon-154G-->A) together with paternal inheritance of a chromosomal microdeletion (Delta1290 bp) encompassing the promoter and the first two exons of the AChRepsilon gene in the index patient. In conclusion, we provide genetic and functional evidence that a mutation of the AChRepsilon subunit promoter (epsilon-154G-->A) causes CMS due to the reduction of gene expression in skeletal muscle. Moreover, this is the first report of a chromosomal microdeletion affecting an AChR gene. This type of mutation may be missed in standard screening techniques of CMS patients.
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http://dx.doi.org/10.1093/brain/awf095DOI Listing
May 2002