TY - JOUR AB - Neuron-restrictive silencer factor/repressor element 1 (RE1)-silencing transcription factor (NRSF/REST) is a transcriptional repressor of a large cluster of neural genes containing RE1 motifs in their promoter region. NRSF/REST is ubiquitously expressed in non-neuronal cells, including astrocytes, while it is downregulated during neuronal differentiation. While neuronal NRSF/REST homeostatically regulates intrinsic excitability and synaptic transmission, the role of the high NRSF/REST expression levels in the homeostatic functions of astrocytes is poorly understood. Here, we investigated the functional consequences of NRSF/REST deletion in primary cortical astrocytes derived from NRSF/REST conditional knockout mice (KO). We found that NRSF/REST KO astrocyte displayed a markedly reduced activity of inward rectifying K+ channels subtype 4.1 (Kir4.1) underlying spatial K+ buffering that was associated with a decreased expression and activity of the glutamate transporter-1 (GLT-1) responsible for glutamate uptake by astrocytes. The effects of the impaired astrocyte homeostatic functions on neuronal activity were investigated by co-culturing wild type hippocampal neurons with NRSF/REST KO astrocytes. Interestingly, neurons experienced increased neuronal excitability at high firing rates associated with decrease afterhyperpolarization and increased amplitude of excitatory postsynaptic currents. The data indicate that astrocytic NRSF/REST directly participates in neural circuit homeostasis by regulating intrinsic excitability and excitatory transmission and that dysfunctions of NRSF/REST expression in astrocytes may contribute to the pathogenesis of neurological disorders. AU - Centonze, E.* AU - Marte, A.* AU - Albini, M.* AU - Rocchi, A.* AU - Cesca, F.* AU - Chiacchiaretta, M.* AU - Floss, T. AU - Baldelli, P.* AU - Ferroni, S.* AU - Benfenati, F.* AU - Valente, P.* C1 - 67204 C2 - 54215 CY - 111 River St, Hoboken 07030-5774, Nj Usa SP - 701-721 TI - Neuron-restrictive silencer factor/repressor element 1-silencing transcription factor (NRSF/REST) controls spatial K+ buffering in primary cortical astrocytes. JO - J. Neurochem. VL - 165 IS - 5 PB - Wiley PY - 2023 SN - 0022-3042 ER - TY - JOUR AB - Delayed cell death in the penumbra region of acute ischemic stroke occurs through apoptotic mechanisms, making it amenable to therapeutic interventions. Fas/CD95 mediates apoptotic cell death in response to external stimuli. In mature neurons, Fas/CD95 signaling is modulated by Fas-apoptotic inhibitory molecule 2 (Faim2), which reduces cell death in animal models of stroke, meningitis, and Parkinson disease. Erythropoietin (EPO) has been studied as a therapeutic strategy in ischemic stroke. Erythropoietin stimulates the phosphatidylinositol-3 kinase/Akt (PI3K/Akt) pathway, which regulates Faim2 expression. Therefore, up-regulation of Faim2 may contribute to neuroprotection by EPO. Male Faim2-deficient mice (Faim2 -/- ) and wild-type littermates (WT) were subjected to 30 min of middle cerebral artery occlusion (MCAo) followed by 72 h of reperfusion. EPO was applied before (30 min) and after (24 and 48 h) MCAo. In WT mice application of EPO at a low dose (5000 U/kg) significantly reduced stroke volume, whereas treatment with high dose (90 000 U/kg) did not. In Faim2 -/- animals administration of low-dose EPO did not result in a significant reduction in stroke volume. Faim2 expression as measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) increased after low-dose EPO but not with high dose. An extensive phenotyping including analysis of cerebral vessel architecture did not reveal confounding differences between the genotypes. In human post-mortem brain Faim2 displayed a differential expression in areas of penumbral ischemia. Faim2 up-regulation may contribute to the neuroprotective effects of low-dose erythropoietin in transient brain ischemia. The dose-dependency may explain mixed effects of erythropoietin observed in clinical stroke trials. AU - Komnig, D.* AU - Gertz, K.* AU - Habib, P.* AU - Nolte, K.W.* AU - Meyer, T.* AU - Brockmann, M.A.* AU - Endres, M.* AU - Rathkolb, B. AU - Hrabě de Angelis, M. AU - German Mouse Clinic Consortium* AU - Schulz, J.B.* AU - Falkenburger, B.H.* AU - Reich, A.* C1 - 53053 C2 - 44364 SP - 258-270 TI - Faim2 contributes to neuroprotection by erythropoietin in transient brain ischemia. JO - J. Neurochem. VL - 145 IS - 3 PY - 2018 SN - 0022-3042 ER - TY - JOUR AB - The diagnosis of Parkinson's disease (PD) still lacks objective diagnostic markers independent of clinical criteria. Cerebrospinal fluid (CSF) samples from 36 PD and 42 age-matched control patients were subjected to inductively coupled plasma-sector field mass spectrometry and a total of 28 different elements were quantified. Different machine learning algorithms were applied to the dataset to identify a discriminating set of elements yielding a novel biomarker signature. Using 19 stably detected elements, the extreme gradient tree boosting model showed the best performance in the discrimination of PD and control patients with high specificity and sensitivity (78.6% and 83.3%, respectively), re-classifying the training data to 100%. The 10 times 10-fold cross-validation yielded a good area under the receiver operating characteristic curve of 0.83. Arsenic, magnesium, and selenium all showed significantly higher mean CSF levels in the PD group compared to the control group (p = 0.01, p = 0.04, and p = 0.03). Reducing the number of elements to a discriminating minimum, we identified an elemental cluster (Se, Fe, As, Ni, Mg, Sr), which most importantly contributed to the sample discrimination. Selenium was identified as the element with the highest impact within this cluster directly followed by iron. After prospective validation, this elemental fingerprint in the CSF could have the potential to be used as independent biomarker for the diagnosis of PD. Next to their value as a biomarker, these data also argue for a prominent role of these highly discriminating six elements in the pathogenesis of PD. (Figure presented.). AU - Maass, F.* AU - Michalke, B. AU - Leha, A.* AU - Boerger, M.* AU - Zerr, I.* AU - Koch, J.C.* AU - Tönges, L.* AU - Bähr, M.* AU - Lingor, P.* C1 - 52858 C2 - 44511 CY - 1200 New York Ave, Nw, Washington, Dc 20005 Usa SP - 342-351 TI - Elemental fingerprint as a cerebrospinal fluid biomarker for the diagnosis of Parkinson's disease. JO - J. Neurochem. VL - 145 IS - 4 PB - Amer Assoc Advancement Science PY - 2018 SN - 0022-3042 ER - TY - JOUR AB - The cerebral cortex is a highly organized structure whose development depends on diverse progenitor cell types, namely apical radial glia, intermediate progenitors, and basal radial glia cells, which are responsible for the production of the correct neuronal output. In recent years, these progenitor cell types have been deeply studied, particularly basal radial glia and their role in cortical expansion and gyrification. We review here a broad series of factors that regulate progenitor behavior and daughter cell fate. We first describe the different neuronal progenitor types, emphasizing the differences between lissencephalic and gyrencephalic species. We then review key factors shown to influence progenitor proliferation versus differentiation, discussing their roles in progenitor dynamics, neuronal production, and potentially brain size and complexity. Although spindle orientation has been considered a critical factor for mode of division and daughter cell output, we discuss other features that are emerging as crucial for these processes such as organelle and cell cycle dynamics. Additionally, we highlight the importance of adhesion molecules and the polarity complex for correct cortical development. Finally, we briefly discuss studies assessing progenitor multipotency and its possible contribution to the production of specific neuronal populations. This review hence summarizes recent aspects of cortical progenitor cell biology, and pinpoints emerging features critical for their behavior. AU - Uzquiano, A.* AU - Gladwyn-Ng, I.* AU - Nguyen, L.A.* AU - Reiner, O.* AU - Götz, M. AU - Matsuzaki, F.* AU - Francis, F.* C1 - 53618 C2 - 44747 CY - 111 River St, Hoboken 07030-5774, Nj Usa SP - 500-525 TI - Cortical progenitor biology: Key features mediating proliferation versus differentiation. JO - J. Neurochem. VL - 146 IS - 5 PB - Wiley PY - 2018 SN - 0022-3042 ER - TY - JOUR AB - For more than 150 years, it is known that occupational overexposure of manganese (Mn) causes movement disorders resembling Parkinson's disease (PD) and PD-like syndromes. However, the mechanisms of Mn toxicity are still poorly understood. Here, we demonstrate that Mn dose- and time-dependently blocks the protein translation of amyloid precursor protein (APP) and heavy-chain Ferritin (H-Ferritin), both iron homeostatic proteins with neuroprotective features. APP and H-Ferritin are post-transcriptionally regulated by iron responsive proteins, which bind to homologous iron responsive elements (IREs) located in the 5 '-untranslated regions (5 '-UTRs) within their mRNA transcripts. Using reporter assays, we demonstrate that Mn exposure repressed the 5 '-UTR-activity of APP and H-Ferritin, presumably via increased iron responsive proteins-iron responsive elements binding, ultimately blocking their protein translation. Using two specific Fe2+-specific probes (RhoNox-1 and IP-1) and ion chromatography inductively coupled plasma mass spectrometry (IC-ICP-MS), we show that loss of the protective axis of APP and H-Ferritin resulted in unchecked accumulation of redox-active ferrous iron (Fe2+) fueling neurotoxic oxidative stress. Enforced APP expression partially attenuated Mn-induced generation of cellular and lipid reactive oxygen species and neurotoxicity. Lastly, we could validate the Mn-mediated suppression of APP and H-Ferritin in two rodent in vivo models (C57BL6/N mice and RjHan:SD rats) mimicking acute and chronic Mn exposure. Together, these results suggest that Mn-induced neurotoxicity is partly attributable to the translational inhibition of APP and H-Ferritin resulting in impaired iron metabolism and exacerbated neurotoxic oxidative stress. AU - Venkataramani, V.* AU - Doeppner, T.R.* AU - Willkommen, D. AU - Cahill, C.M.* AU - Xin, Y.* AU - Ye, G.* AU - Liu, Y.* AU - Southon, A.* AU - Aron, A.* AU - Au-Yeung, H.Y.* AU - Huang, X.* AU - Lahiri, D.K.* AU - Wang, F.* AU - Bush, A.I.* AU - Wulf, G.G.* AU - Ströbel, P.* AU - Michalke, B. AU - Rogers, J.T.* C1 - 54196 C2 - 45432 CY - 111 River St, Hoboken 07030-5774, Nj Usa SP - 831-848 TI - Manganese causes neurotoxic iron accumulation via translational repression of amyloid precursor protein and H-Ferritin. JO - J. Neurochem. VL - 147 IS - 6 PB - Wiley PY - 2018 SN - 0022-3042 ER - TY - JOUR AU - Darovic, S.* AU - Stalekar, M.* AU - Lee, Y.-B.* AU - Pohleven, J.* AU - Modic, M. AU - Fonovic, M.* AU - Turk, B.* AU - Drukker, M. AU - Shaw, C.E. AU - Rogelj, B.* C1 - 49672 C2 - 40799 CY - Hoboken SP - 415-415 TI - Intranuclear (GGGGCC)(n) RNA foci induce formation of paraspeckle-like structures. JO - J. Neurochem. VL - 138 PB - Wiley-blackwell PY - 2016 SN - 0022-3042 ER - TY - JOUR AB - Dopaminergic neurons in the ventral mesencephalon (= the ventral mesencephalic dopaminergic complex) are known for their role in a multitude of behaviors, including cognition, reward, addiction and voluntary movement. Dysfunctions of these neurons are the underlying cause of various neuropsychiatric disorders, such as depression, addiction and schizophrenia. In addition, Parkinson's disease (PD), which is the second most common degenerative disease in developed countries, is characterized by the degeneration of dopaminergic neurons, leading to the core motor symptoms of the disease. However, only a subset of dopaminergic neurons in the ventral mesencephalon is highly vulnerable to the disease process. Indeed, research over several decades revealed that the neurons in the ventral mesencephalic dopaminergic complex do not form a homogeneous group with respect to anatomy, physiology, function, molecular identity or vulnerability/dysfunction in different diseases. Here, we review how the concept of dopaminergic neuron diversity, assisted by the advent and application of new technologies, evolved and was refined over time and how it shaped our understanding of PD pathogenesis. Understanding this diversity of neurons in the ventral mesencephalic dopaminergic complex at all levels is imperative for the development of new and more selective drugs for both PD and various other neuropsychiatric diseases. AU - Vogt Weisenhorn, D.M. AU - Giesert, F. AU - Wurst, W. C1 - 48756 C2 - 41329 CY - Hoboken SP - 8-26 TI - Diversity matters - heterogeneity of dopaminergic neurons in the ventral mesencephalon and its relation to Parkinson's disease. JO - J. Neurochem. VL - 139 PB - Wiley-blackwell PY - 2016 SN - 0022-3042 ER - TY - JOUR AU - Xiang, X.* AU - Werner, G.* AU - Bohrmann, B.* AU - Mazaheri, F.* AU - Capell, A.* AU - Feederle, R.* AU - Knuesel, I. AU - Kleinberger, G.* AU - Haass, C.* C1 - 49669 C2 - 40817 CY - Hoboken SP - 422-422 TI - TREM2-deficiency reduces the efficacy of immunotherapeutic amyloid clearance. JO - J. Neurochem. VL - 138 PB - Wiley-blackwell PY - 2016 SN - 0022-3042 ER - TY - JOUR AB - Subretinal injections with glial cell line-derived neurotrophic factor (GDNF) rescue morphology as well as function of rod cells in mouse and rat animal models of Retinitis pigmentosa. At the same time, it is postulated that this effect is indirect, mediated by activation of retinal Müller glial (RMG) cells. Here we show that Cyr61/CCN1, one of the secreted proteins upregulated in primary RMG after GDNF stimulation, provides neuroprotective and pro-survival capacities: Recombinant Cyr61 significantly reduced photoreceptor cells (PR) death in organotypic cultures of Pde6brd1 retinas. In order to identify stimulated pathways in the retina, we treated Pde6brd1 retinal explants with Cyr61 and observed an overall increase in activated Erk1/2 and Stat3 signalling molecules characterized by activation-site specific phosphorylation. To identify Cyr61 retinal target cells, we isolated primary porcine PR, RMG and retinal pigment epithelium (RPE) cells and exposed them separately to Cyr61. Here, RMG as well as RPE cells responded with induced phosphorylation of Erk1/2, Stat3, and Akt. In PR, no increase in phosphorylation in any of the studied proteins was detected, suggesting an indirect neuroprotective effect of Cyr61. Cyr61 may thus act as an endogenous pro-survival factor for PR, contributing to the complex repertoire of neuroprotective activities generated by RMG and RPE cells. AU - Kucharska, J. AU - del Río, P. AU - Arango-González, B.* AU - Gorza, M. AU - Feuchtinger, A. AU - Hauck, S.M. AU - Ueffing, M. C1 - 30755 C2 - 33833 CY - Hoboken SP - 227-240 TI - Cyr61 activates retinal cells and prolongs photoreceptor survival in rd1 mouse model of retinitis pigmentosa. JO - J. Neurochem. VL - 130 IS - 2 PB - Wiley-blackwell PY - 2014 SN - 0022-3042 ER - TY - JOUR AB - Dendritic targeting of mRNAs encoding the microtubule-associated protein 2 (MAP2) in neurons involves a cis-acting dendritic targeting element. Two rat brain proteins, MARTA1 and MARTA2, bind to the cis-element with both high affinity and specificity. In this study, affinity-purified MARTA2 was identified as orthologue of human far-upstream element binding protein 3. In neurons, it resides in somatodendritic granules and dendritic spines and associates with MAP2 mRNAs. Expression of a dominant-negative variant of MARTA2 disrupts dendritic targeting of endogenous MAP2 mRNAs, while not noticeably altering the level and subcellular distribution of polyadenylated mRNAs as a whole. Finally, MAP2 transcripts associate with the microtubule based motor KIF5 and inhibition of KIF5 but not cytoplasmic dynein function disrupts extrasomatic trafficking of MAP2 mRNA granules. Thus, in neurons MARTA2 appears to represent a key trans-acting factor involved in KIF5c-mediated dendritic targeting of MAP2 mRNAs. AU - Zivraj, K.H.* AU - Rehbein, M.* AU - Olschläger-Schütt, J.* AU - Schob, C.* AU - Falley, K.* AU - Buck, F.* AU - Schweizer, M.* AU - Schepis, A.* AU - Kremmer, E. AU - Richter, D.* AU - Kreienkamp, H.J.* AU - Kindler, S.* C1 - 11596 C2 - 30707 SP - 670-684 TI - The RNA-binding protein MARTA2 regulates dendritic targeting of MAP2 mRNAs in rat neurons. JO - J. Neurochem. VL - 124 IS - 5 PB - Wiley-Blackwell PY - 2013 SN - 0022-3042 ER - TY - JOUR AB - Huntington's disease (HD) is a devastating neurodegenerative disorder caused by an expansion of CAG trinucleotide repeats encoding for polyglutamine (polyQ) in the huntingtin (Htt) gene. Despite considerable effort, the mechanisms underlying the toxicity of the mutated Htt protein remains largely uncertain. To identify novel therapeutic targets, we recently employed the approach of tandem affinity purification and discovered that calretinin (Cr), a member of the EF-hand family of calcium-binding proteins, is preferentially associated with mHtt, although it also interacts with wild-type Htt. These observations were supported by coimmunoprecipitation and by colocalization of Cr with mHtt in neuronal cultures. Over- expression of Cr reduced mHtt-caused cytotoxicity in both non-neuronal and neuronal cell models of HD, whereas knockdown of Cr expression in the cells enhanced mHtt-caused neuronal cell death. In addition, over-expression of Cr was also associated with reduction of intracellular free calcium and activation of Akt. These results suggest that Cr may be a potential therapeutic target for treatment of HD. AU - Dong, G.* AU - Gross, K.* AU - Qiao, F.* AU - Ferguson, J.* AU - Callegari, E.A.* AU - Rezvani, K.* AU - Zhang, D.* AU - Gloeckner, C.J. AU - Ueffing, M. AU - Wang, H.* C1 - 11049 C2 - 30479 SP - 437-446 TI - Calretinin interacts with huntingtin and reduces mutant huntingtin-caused cytotoxicity. JO - J. Neurochem. VL - 123 IS - 3 PB - Wiley-Blackwell PY - 2012 SN - 0022-3042 ER - TY - JOUR AB - Neuronal and glial deposition of misfolded, proteolytically processed, polyubiquitinated and abnormally phosphorylated C-terminal fragments (CTFs) of the TAR DNA binding protein-43 (TDP-43) is a pathological hallmark of frontotemporal lobar degeneration with ubiquitin positive inclusions (FTLD-U) and certain cases of amyotrophic lateral sclerosis. We demonstrate that TDP-43 can be proteolytically processed by caspases upon induction of apoptosis to a major 35 kDa and a minor 25 kDa CTF. These fragments are initially soluble, but over time they accumulate as insoluble and pathologically phosphorylated derivatives. However, proteolytic processing appears not to be absolutely required for the deposition of insoluble TDP-43 species, since a caspase resistant mutant of TDP-43 is also converted into insoluble species. Phosphorylation at S409/410 apparently occurs late during the conversion of soluble to insoluble TDP-43, suggesting that phosphorylation is not a prerequisite for aggregation. Loss of function of the progranulin (PGRN) gene causes FTLD-U with TDP-43 positive inclusions and has been suggested to lead to caspase activation and subsequent TDP-43 processing. However, siRNA-mediated knockdown of PGRN in cell culture as well as a PGRN gene knockout in mice failed to cause the formation of the disease characterizing CTFs of TDP-43. Our findings therefore suggest that caspase-mediated processing generates CTFs of similar biochemical properties as those occurring in nuclear and cytoplasmic deposits of FTLD-U patients independent of PGRN levels. AU - Dormann, D.* AU - Capell, A.* AU - Carlson, A.M.* AU - Shankaran, S.S.* AU - Rodde, R.* AU - Neumann, M.* AU - Kremmer, E. AU - Matsuwaki, T.* AU - Yamanouchi, K.* AU - Nishihara, M.* AU - Haass, C.* C1 - 1632 C2 - 26510 SP - 1082-1084 TI - Proteolytic processing of TAR DNA binding protein-43 by caspases produces C-terminal fragments with disease defining properties independent of progranulin. JO - J. Neurochem. VL - 110 IS - 3 PB - Wiley-Blackwell Publishing, Inc PY - 2009 SN - 0022-3042 ER - TY - JOUR AB - Autosomal dominant mutations in the human Leucine-Rich Repeat Kinase 2 (LRRK2) gene represent the most common monogenetic cause of Parkinson disease (PD) and increased kinase activity observed in pathogenic mutants of LRRK2 is most likely causative for PD-associated neurotoxicity. The sequence of the LRRK2 kinase domain shows similarity to MAP kinase kinase kinases. Furthermore, LRRK2 shares highest sequence homology with mixed linage kinases which act upstream of canonical MAPKK and are involved in cellular stress responses. Therefore, we addressed the question if LRRK2 exhibits MAPKKK activity by systematically testing MAPKKs as candidate substrates, in vitro. We demonstrate that LRRK2 variants phosphorylate mitogen-activated protein kinase kinases (MAPKK), including MKK3 -4, -6 and -7. MKKs act upstream of the MAPK p38 and JNK mediating oxidative cell stress, neurotoxicity and apoptosis. The disease-associated LRRK2 G2019S and I2020T mutations show an increased phosphotransferase activity towards MKKs correlating with the activity shown for its autophosphorylation. Our findings present evidence of a new class of molecular targets for mutant LRRK2 that link to neurotoxicity, cellular stress, cytoskeletal dynamics and vesicular transport. AU - Gloeckner, C.J. AU - Schumacher, A. AU - Boldt, K. AU - Ueffing, M. C1 - 2232 C2 - 26958 SP - 959-968 TI - The Parkinson disease-associated protein kinase LRRK2 exhibits MAPKKK activity and phosphorylates MKK3/6 and MKK4/7, in vitro. JO - J. Neurochem. VL - 109 IS - 4 PB - Wiley-Blackwell PY - 2009 SN - 0022-3042 ER - TY - JOUR AB - Photoreceptor degeneration in retinitis pigmentosa is one of the leading causes of hereditary blindness in the developed world. Although causative genetic mutations have been elucidated in many cases, the underlying neuronal degeneration mechanisms are still unknown. Here, we show that activation of cGMP-dependent protein kinase (PKG) hallmarks photoreceptor degeneration in rd1 and rd2 human homologous mouse models. When induced in wild-type retinae, PKG activity was both necessary and sufficient to trigger cGMP-mediated photoreceptor cell death. Target-specific, pharmacological inhibition of PKG activity in both rd1 and rd2 retinae strongly reduced photoreceptor cell death in organotypic retinal explants. Likewise, inhibition of PKG in vivo, using three different application paradigms, resulted in robust photoreceptor protection in the rd1 retina. These findings suggest a pivotal role for PKG activity in cGMP-mediated photoreceptor degeneration mechanisms and highlight the importance of PKG as a novel target for the pharmacological intervention in RP. AU - Paquet-Durand, F.* AU - Hauck, S.M. AU - van Veen, T.* AU - Ueffing, M. AU - Ekström, P.* C1 - 1487 C2 - 26896 SP - 796-810 TI - PKG activity causes photoreceptor cell death in two retinitis pigmentosa models. JO - J. Neurochem. VL - 108 IS - 3 PB - Blackwell Publishing PY - 2009 SN - 0022-3042 ER - TY - JOUR AB - Delta-like 1 (Dlk1), a member of the Delta/Notch protein family, is expressed in the mouse ventral midbrain (VM) as early as embryonic day 11.5 (E11.5) followed by exclusive expression in tyrosine 3-monooxygenase (TH) positive neurons from E12.5 onwards. To further elucidate the yet unknown function of Dlk1 in VM neuron development, we investigated the effect of soluble Dlk1 protein as well as the intrinsic Dlk1 function in the course of VM progenitor expansion and dopaminergic (DA) neuron differentiation in vitro. Dlk1 treatment during expansion increased DA progenitor proliferation and the proportion of NR4A2+ neurons expressing TH after differentiation, whereas Dlk1 treatment during the course of DA precursor differentiation did not alter TH+ neuron counts. In contrast, silencing of endogenously expressed Dlk1 prior to DA precursor differentiation partially prevented the expression of DA neuron markers, which was not accompanied with alteration of overall or local proliferation. Due to the latter finding in combination with the absence of Dlk1 negative DA neurons in differentiated cultures, we suggest that Dlk1 expression might have a permissive effect on DA neuron differentiation in vitro. The study presented here is the first publication identifying Dlk1 effects on ventral midbrain-derived DA precursor differentiation. AU - Bauer, M. AU - Szulc, J.* AU - Meyer, M.* AU - Jensen, C.H.* AU - Terki, T.A.* AU - Meixner, A. AU - Kinkl, N. AU - Gasser, T.* AU - Aebischer, P.* AU - Ueffing, M. C1 - 1492 C2 - 25770 SP - 1101-1115 TI - Delta-like 1 participates in the specification of ventral midbrain progenitor derived dopaminergic neurons. JO - J. Neurochem. VL - 104 IS - 4 PB - Wiley-Blackwell PY - 2008 SN - 0022-3042 ER - TY - JOUR AB - Epithelial sodium channel (ENaC) is a member of the ENaC/degenerin family of amiloride-sensitive, non-voltage gated sodium ion channels. ENaC alpha, beta and gamma subunits are abundantly expressed in epithelial tissues, where they have been well characterized. An ENaC delta subunit has also been described in the human nervous system, although its histological distribution pattern remains unexplored. We have now isolated a novel ENaC delta isoform (delta2) from human brain and studied the expression pattern of both the known (delta1) and the new (delta2) isoforms in the human and monkey telencephalon. ENaC delta2 is produced by a combination of alternative transcription start sites, a frame shift in exon 3 and alternative splicing of exon 4. It forms functional amiloride-sensitive sodium channels when co-expressed with ENaC beta and gamma accessory subunits. Comparison with the classical ENaC channel (alphabetagamma) indicates that the interaction between delta2, beta and gamma is functionally inefficient. Both ENaC delta isoforms are widely expressed in pyramidal cells of the human and monkey cerebral cortex and in different neuronal populations of telencephalic subcortical nuclei, but double-labelling experiments demonstrated a low level of co-localization between isoforms (5-8%), suggesting specific functional roles for each of them. AU - Giraldez, T.* AU - Afonso-Oramas, D.* AU - Cruz-Muros, I.* AU - Garcia-Marin, V.* AU - Pagel, P. AU - González-Hernández, T.* AU - Alvarez de la Rosa, D.* C1 - 3876 C2 - 24913 SP - 1304-1315 TI - Cloning and functional expression of a new epithelial sodium channel delta subunit isoform differentially expressed in neurons of the human and monkey telencephalon. JO - J. Neurochem. VL - 102 IS - 4 PB - Blackwell PY - 2007 SN - 0022-3042 ER - TY - JOUR AU - Paquet-Durand, F.* AU - Azadi, S.* AU - Hauck, S.M. AU - Ueffing, M. AU - van Veen, T.* AU - Ekström, P.* C1 - 2178 C2 - 23627 SP - 802-814 TI - Calpain is activated in degenerating photoreceptors in the rd1 mouse. JO - J. Neurochem. VL - 96 PY - 2006 SN - 0022-3042 ER - TY - JOUR AU - Bauer, M. AU - Suppmann, S. AU - Meyer, M.* AU - Hesslinger, C.* AU - Gasser, T.* AU - Widmer, H.R.* AU - Ueffing, M. C1 - 22010 C2 - 20557 SP - 1300-1310 TI - Glial cell line-derived neurotrophic factor up-regulates GTP-cyclohydrolase I activity and tetrahydrobiopterin levels in primary dopaminergic neurones. JO - J. Neurochem. VL - 82 PY - 2002 SN - 0022-3042 ER -