A5080305063- Nerve injury and regeneration
- Neurogenesis and neuroplasticity mechanisms
- Cell death mechanisms and regulation
- Signaling Pathways in Disease
- Axon Guidance and Neuronal Signaling
- RNA Interference and Gene Delivery
- Neuroscience and Neuropharmacology Research
- Endoplasmic Reticulum Stress and Disease
- Neuroblastoma Research and Treatments
- Autophagy in Disease and Therapy
- Neuropeptides and Animal Physiology
- Cellular transport and secretion
- Adenosine and Purinergic Signaling
- Nuclear Receptors and Signaling
- Virus-based gene therapy research
- Mitochondrial Function and Pathology
- RNA Research and Splicing
- Venomous Animal Envenomation and Studies
- Healthcare and Venom Research
- Renal and related cancers
- Hearing, Cochlea, Tinnitus, Genetics
- Viral Infectious Diseases and Gene Expression in Insects
- Vestibular and auditory disorders
- Cancer-related Molecular Pathways
- Toxin Mechanisms and Immunotoxins
University of Helsinki
2008-2018
Tallinn University of Technology
2013-2018
Helsinki Institute of Physics
1994-2011
Biocenter Finland
1999-2010
Estonian Academy of Sciences
1987-1994
ABSTRACT The shapes of different organs can be explained largely by two fundamental characteristics their epithelial rudiments – the pattern branching and rate pro-liferation. Glial-cell-line-derived neurotrophic factor (GDNF) has recently been implicated in development metanephric ureteric epithelium (Pichel, J. G., Shen, L., Sheng, H. Z., Granholm, A.-C., Drago, J., Grinberg, A., Lee, E. Huang, S. P., Saarma, M., Hoffer, B.J., Sariola, Westphal, (1996). Nature 382, 73-76; Sánchez, M.P.,...
In situ hybridization was used to study the site and timing of expression nerve growth factor (NGF), brain-derived neurotrophic (BDNF), neurotrophin 3 (NT-3), 5 (NT-5) mRNAs in developing inner ear rat. sensory epithelia, levels NGF NT-5 were below detection limit. NT-3 BDNF expressed otic vesicle overlapping but also distinct regions. Later development, transcripts localized differentiating supporting cells auditory organ vestibular maculae. these intensity mRNA decreased parallel with...
Nerve growth factor receptor (NGFR) serves as the binding site for neurotrophic factors. Although NGFR has been found in several embryonic tissues outside nervous system, function of embryogenesis non-neuronal organs remains unknown. is transiently synthesized by rat kidney and disappears from nephrons upon their terminal differentiation. Anti-sense oligonucleotide inhibition expression inhibits morphogenesis. Therefore, required not only development but also differentiation tubules.
Glial cell line‐derived neurotrophic factor (GDNF) has potentially great clinical importance in the treatment of Parkinson's disease and several other neurodegenerative diseases, however its intracellular signaling mechanisms are poorly understood. Here we show that upon GDNF binding glycosyl‐phosphatidylinositol (GPI)‐linked receptor α1 (GFRα1) activates cytoplasmic Src family tyrosine kinase(s) Ret kinase‐deficient cultured mouse dorsal root ganglion neurons two Ret‐negative lines....
Abstract The localization of glial cell line‐derived neurotrophic factor (GDNF) mRNA was studied by in situ hybridization rat from embryonic (E) day E10 to E15. At E10, GDNF is found the urogenital field and cranial part gut. E11, most abundant expression seen epithelial cells second, third fourth pharyngeal pouches, arches pharynx. Also mesenchymal gut mesonephric tubules contain mRNA. E13, observed layers oesophagus, intestine stomach, around condensing cartilages metanephric kidney...
Delayed delivery of MANF to rat brain after ischemic stroke promotes functional recovery and recruits phagocytic immune cells.
Glial cell line-derived neurotrophic factor (GDNF) is a potent for several populations of CNS and peripheral neurons. Synthesis storage GDNF by the neuron-like adrenal medullary cells suggest roles in functions and/or maintenance spinal cord neurons that innervate medulla. We show unilateral adrenomedullectomy causes degeneration all sympathetic preganglionic within intermediolateral column (IML) segments T7-T10 project to In situ hybridization revealed IML express...
Glial cell line-derived neurotrophic factor (GDNF) family ligands signal through receptor complex consisting of a glycosylphosphatidylinositol-linked GDNF (GFR) α subunit and the transmembrane tyrosine kinase RET. The inherited cancer syndrome multiple endocrine neoplasia type 2 (MEN2), associated with different mutations in RET, is characterized by medullary thyroid carcinoma. signals via GFRα1, neurturin GFRα2, artemin GFRα3, whereas mammalian GFRα for persephin (PSPN) unknown. Here we...
The TrkC/NT-3 receptor/ligand pair is believed to be part of the classic neurotrophic theory claiming that neuronal death occurs by default when factors become limited, through loss survival signals. Here, we show TrkC a dependence receptor and, as such, induces caspase-dependent apoptotic in absence NT-3 immortalized cells, proapoptotic activity inhibited presence NT-3. This relies on caspase-mediated cleavage intracellular domain TrkC, which permits release fragment. fragment apoptosis...
The discovery of RNA interference (RNAi) has revolutionized biological research and a huge potential for therapy. Since small double-stranded RNAs (dsRNAs) are required various RNAi applications, there is need cost-effective methods producing large quantities high-quality dsRNA. We present two novel, flexible virus-based systems the efficient production dsRNA: (1) an in vitro system utilizing combination T7 polymerase RNA-dependent (RdRP) bacteriophage ϕ6 to generate dsRNA molecules...
Injured neurons become dependent on trophic factors for survival. However, application of to the site injury is technically extremely challenging. Novel approaches are needed circumvent this problem. Here, we unravel mechanism emergence dependency injured brain-derived neurotrophic factor (BDNF) Based mechanism, propose use diuretic bumetanide prevent requirement BDNF and consequent neuronal death in areas. Responses neurotransmitter GABA change from hyperpolarizing intact depolarizing...
Abstract Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a prosurvival protein that protects the cells when applied intracellularly in vitro or extracellularly vivo . Its protective mechanisms are poorly known. Here we studied role of two short sequence motifs within carboxy-(C) terminal domain MANF its neuroprotective activity: CKGC (a CXXC motif) could be involved redox reactions, and C-terminal RTDL sequence, an endoplasmic reticulum (ER) retention signal. We mutated these...
We have identified and characterized N-Bak, a neuron-specific isoform of the pro-apoptotic Bcl-2 family member Bak. N-Bak is generated by splicing novel 20-base pair exon, which changes previously described Bak, containing homology (BH) domains BH1, BH2, BH3, into shorter BH3-only protein. As demonstrated reverse transcription-polymerase chain reaction RNase protection assay, transcripts are expressed only in central peripheral neurons, but not other cells, whereas Bak ubiquitously, neurons....
We examined the expression of neurotrophins (NTFs) and their receptor mRNAs in rat trigeminal ganglion first branchial arch before at time maxillary nerve growth. The appears embryonic day (E)10 reaches epithelium E12, as revealed by anti-L1 immunohistochemistry. In situ hybridization demonstrates, that E10-E11, neurotrophin-3 (NT-3) mRNA is expressed mainly mesenchyme, but neurotrophin-4 (NT-4) arch. NGF brain-derived neurotrophic factor (BDNF) start to be distal part brachial shortly its...
To analyze the roles of neurotrophins during early development rat teeth, we studied expression neurotrophin mRNAs from initiation first molar formation to completion crown morphogenesis. With RNAase protection assay all were detected in embryonic teeth. In situ hybridization analysis revealed developmentally changing, distinct patterns for nerve growth factor (NGF) and neurotrophin-3 (NT-3), which shown not be regulated by or dependent on peripheral innervation. NGF appeared mesenchymal...
Mammalian MANF and CDNF proteins are evolutionarily conserved neurotrophic factors that can protect repair mammalian dopaminergic neurons in vivo. In Drosophila, the sole protein (DmManf) is needed for maintenance of neurites dopamine levels. Although both secreted intracellular roles have been demonstrated, very little known about molecular mechanism their action. Here, by using a transgenic rescue approach DmManf mutant background we show only full-length containing amino-terminal...
Abstract Cerebral dopamine neurotrophic factor (CDNF) protects the nigrostriatal dopaminergic (DA) neurons in rodent models of Parkinson’s disease and restores DA circuitry when delivered after these have begun to degenerate. These been suggested transport striatal CDNF retrogradely substantia nigra (SN). However, cultured cells binding internalization extracellular has not reported. The first aim this study was examine cellular localization pharmacokinetic properties recombinant human...