Adresse: Albert Einstein Allee 11
89081 Ulm
E-mail: andreas.grabrucker@alumni.uni-ulm.de


AG Molekulare Analyse von Synaptopathien

Using a combination of biochemical, cellular, molecular and reverse genetic approaches, we investigate proteins of excitatory postsynapses, specifically scaffold proteins of the ProSAP/Shank family. These proteins play fundamental roles in the nascent assembly and function of glutamatergic synapses. More recently, it has become evident that members of the ProSAP/Shank families are linked to Autism Spectrum Disorders, Alzheimers disease and schizophrenia. We are interested in questions related to the dynamics of synapse and PSD scaffold formation. For example, once a synapse is formed, do the proteins that comprise the junction exchange and on what time scale (seconds to hours, days, months or years)? How do these exchange kinetics relate to the life-time of individual synapses? What mechanisms regulate synapse stability and elimination (Zinc-ion concentrations, signaling pathways)?

Understanding how these factors contribute to synaptic function will allow the development of rational research strategies to normalize function in individuals with synaptopathies. To that end, the use of novel drug carriers (i.e. Nanoparticles) and their characterization in regard of their potency to influence synapse formation, maturation and plasticity has become a central part of our research.

"Naturwissenschaft. Diplom/Masterarbeiten und mediz. Doktorarbeiten zu vergeben".

Verzeichnis wissenschaftlicher Publikationen  

1. GRABRUCKER AM, VAIDA B, BOCKMANN J, BOECKERS TM: Efficient targeting of proteins to postsynaptic densities of excitatory synapses using a novel pSDTarget vector system. Journal of Neuroscience Methods. 2009, 181(2):227-34.

2. SCHMEISSER* JM, GRABRUCKER* AM, BOCKMANN J, BOECKERS TM: Synaptic crosstalk between NMDA receptors and LAPSER1/ß-catenin at excitatory synapses. J Biol Chem. 2009, 16;284(42):29146-5

3. GRABRUCKER AM, VAIDA B, BOCKMANN J, BOECKERS TM: Synaptogenesis of hippocampal neurons in primary cell culture, Cell and Tissue Research. 2009, 338:333–341

4. VELLANKI SH, GRABRUCKER A, LIEBAU S, PROEPPER C, ERAMO A, BRAUN V, BOECKERS T, DEBATIN KM, FULDA S: Small molecule XIAP inhibitors enhance gamma- irradiation-induced apoptosis in preclinical models of glioblastoma. Neoplasia. 2009, 11(8):743-52.

5. Grabrucker AM, Knight MJ, Proepper C, Bockmann J, Joubert M, Rowan M, Nienhaus GU, Garner CC, Bowie JU, Kreutz MR, Gundelfinger ED, Boeckers TM: Concerted action of zinc and ProSAP/Shank in synaptogenesis and synapse maturation. EMBO Journal 2011, 30 (3): 569-81.

6. Grabrucker AM, Garner CC, Boeckers TM, Bondioli L, Ruozi B, Forni F, Vandelli MA, Tosi G: Development of novel Zn2+ loaded nanoparticles designed for cell-type targeted drug release in CNS neurons: in vitro evidences. Plos One 2011, 6 (3): e17851.

7. GRABRUCKER AM, ROWAN M, GARNER CC: Brain-delivery of Zinc-ions as potential treatment for neurological diseases. Drug Delivery Letters 2011 [in press]

8. GRABRUCKER AM, SCHMEISSER MJ, SCHOEN M, BOECKERS TM: Postsynaptic ProSAP/Shank scaffolds in the cross-hair of synaptopathies. Trends in Cell Biology 2011

9. GRABRUCKER AM*, SCHMEISSER MJ*, UDVARDI PT, ROWAN M, SCHOEN M, WOODLING NS, ANDREASSON KI, HOF PR, BUXBAUM JD, GARNER CC, BOECKERS TM: Amyloid beta protein-induced zinc sequestration leads to synaptic loss via dysregulation of the ProSAP2/Shank3 scaffold. Mol. Neurodeg. 2011

10. Tosi G, Fano RA, Badiali L, Bondioli L, Ruozi B, Belletti B, Vergoni A, Rivasi F, Benassi R, Grabrucker AM, Vandelli MA, Forni F: Peptide-engineered polylactide-co-glycolide (PLGA) nanoparticles for brain delivery of drugs: in vivo experiments and proof of concept, Journal of Nanoscience and Nanotechnology, 2011 [in press].