Skip to content

Prof. Dr. Herbert Zimmermann

Campus Riedberg, Biologicum
Institute of Cell Biology and Neuroscience
Molecular and Cellular Neurobiology
Max-von-Laue-Str. 13 (Fluegel A, 1. OG, Room 1.122)
D-60438 Frankfurt am Main

Tel +49 (0)69 798 42036
Fax +49 (0)69 798 42021



Scientific Focus

Nucleotide signalling, adult neurogenesis
ATP and other nucleotides such as ADP, UTP, UDP, or the diadenosine polyphosphates Ap4A and Ap5A act as signalling substances in the nervous system. Their action is mediated by specific receptors and terminated by hydrolysis via surface-located enzymes (ectonucleotidases) that eventually break down the nucleotides to the respective nucleoside. We are studying the molecular biology, functional properties and cellular distribution of the various ectonucleotidases. More recently we began to analyze the role of ectonucleotidases and nucleotide signalling in the control of the formation of nerve cells from stem cells in the adult brain (adult neurogenesis). Adult neural stem cells express the ectonucleotidase NTPDase2. Activation of nucleotide receptors (P2 receptors) stimulates progenitor cell proliferation synergistically with growth factors. The molecular processes underlying this interaction and their functional consequences for regulating adult neurogenesis are under study using in both in vivo and in vitro.

Synaptic vesicle proteomics
Neurotransmitter substances are stored in synaptic vesicles and released on stimulation and the gated influx of calcium ions. This process is highly regulated by molecular machinery invovling synaptic vesicle proteins equally well as soluble proteins of the nerve terminal and proteins of the presynaptic plasma membrane. More recently, together with Walter Volknandt, a proteomics approach was launched for the identification of novel synaptic proteins from murine brain using immunoaffinity isolation of synaptic vesicles followed by separation of vesicle proteins using one- and two-dimensional polyacrylamide gel electrophoresis and a combination of matrix assisted laser desorption ionization – time of flight mass spectrometry (MALDI-TOF-MS) and nano-electrospray ionization tandem mass spectrometry (nano-LC ESI-MS/MS). The work aims at the functional and molecular characterization of the identified synaptic vesicle proteins.


Cell and tissue culture, immunocytochemistry including confocal microscopy, in situ hybridization, general molecular biological techniques, including molecular cloning, PCR, cell transfection, analysis of expressed proteins, general protein biochemical techniques, including immunoaffinity purification, immunoblotting, separation of membrane proteins by one and two dimensional gel electrophoresis (including blue native PAGE, BAC/SDS-PAGE and dSDS-PAGE), isolation of neural stem cells, culturing and analysis of neurospheres, in vitro and in vivo differentiation of stem cells.

Selected Publications

Stefani J, Tschesnokowa O, Parrilla M, Robaye B, Boeynaems JM, Acker-Palmer A, Zimmermann H, Gampe K. (2018) Disruption of the microglial ADP receptor P2Y13 enhances adult hippocampal neurogenesis. Front Cell Neurosci. 12:134. doi: 10.3389/fncel.2018.00134

Pleli T, Mondorf A, Ferreiros N, Thomas D, Dvorak K, Biondi RM, Heringdorf DMZ, Zeuzem S, Geisslinger G, Zimmermann H, Waidmann O, Piiper A. (2018) Activation of Adenylyl Cyclase Causes Stimulation of Adenosine Receptors. Cell Physiol Biochem. 45(6):2516-2528. doi: 10.1159/000488270

Junker A, Renn C, Dobelmann C, Namasivayam V, Jain S, Losenkova K, Irjala H, Duca S, Balasubramanian R, Chakraborty S, Börgel F, Zimmermann H, Yegutkin GG, Müller CE, Jacobson KA. (2019) Structure-Activity Relationship of Purine and Pyrimidine Nucleotides as Ecto-5′-Nucleotidase (CD73) Inhibitors. J Med Chem. 2019 Apr 11;62(7):3677-3695. doi: 10.1021/acs.jmedchem.9b00164. Epub 2019 Mar 21. PMID: 30895781

Zimmermann, H. (2020) History of ectonucleotidases and their role in purinergic signaling. Biochem Pharmacol. 6:114322. doi: 10.1016/j.bcp.2020.114322.

Bhattarai S, Pippel J, Scaletti ER, Idris R, Freundlieb M, Rolshoven G, Renn C, Lee SY, Abdelrahman A, Zimmermann H, El-Tayeb A, Müller CE, Sträter N (2020) 2-Substituted α,β Methylene-ADP Derivatives: Potent Competitive Ecto-5′-nucleotidase (CD73) Inhibitors with Variable Binding Modes. J Med Chem. 2020 Mar 26;63(6):2941-2957. doi: 10.1021/acs.jmedchem.9b01611

Back To Top