Klaus Armin Nave

..Loss of glial support causes progressive axon degeneration and possibly local inflammation, both of which are likely to contribute to a variety of neuronal diseases in the central and peripheral nervous systems...

..Whether this signaling system operates in central nervous system myelination remains an open question of major importance for human demyelinating diseases...

..But putting the miRNA brake on oligodendrocyte gene expression is required throughout life...

..This glial support of axonal integrity may be relevant for a number of neurological and psychiatric diseases...

..This function may be independent of myelin itself. Myelin abnormalities cause a number of neurological diseases, and may also contribute to complex neuropsychiatric disorders...

..Transgenic animal models have become essential for dissecting CMT disease mechanisms and exploring novel therapies...

..This shows that cholesterol is an indispensable component of myelin membranes and that cholesterol availability in oligodendrocytes is a rate-limiting factor for brain maturation...

..We suggest that Rab3A may regulate SNAP-29-mediated membrane fusion during myelination...

..This study highlights both the flexibility and the limits of horizontal cholesterol transfer in vivo and may have implications for the understanding of neurodegenerative diseases...

..We suggest a model by which myelin-forming Schwann cells integrate axonal Nrg1 signals as a biochemical measure of axon size...

..Together, these findings reveal a role of endogenous EPO/EPOR for cognition, at least in schizophrenic patients...

..We suggest a model in which loss of axonal contact triggers denervated Schwann cells to transiently express NRG1 as an autocrine/paracrine signal that promotes Schwann cell differentiation and remyelination...

..In particular, the specific contribution of risk or candidate gene variants to the complex schizophrenic phenotype is largely unknown...

..Dietary cholesterol did not reduce Plp1 overexpression but facilitated incorporation of PLP into myelin membranes. These findings may have implications for therapeutic interventions in patients with PMD...

..However, the critical EPO targets in brain are unknown, and separation of direct and indirect effects has remained difficult, given the role of EPO in hematopoiesis and brain oxygen supply...

..Because myelinated axons can use lactate when energy-deprived, our findings suggest a model in which axon-glia metabolic coupling serves a physiological function...

..Oligodendrocyte dysfunction, such as that in multiple sclerosis lesions, may suffice to cause secondary axonal loss...

..That myelin synthesis is not restricted to early development but can occur later in life is relevant to developmental disorders and myelin disease...

..The NeuroD(loxP) mouse mutant will be a valuable tool to study the developmental and adult function of NeuroD in nervous system and pancreas...

..Our findings define a new stage in corpus callosum development and demonstrate that neocortical projection neurons require transcriptional specification by neuronal bHLH proteins to execute an intrinsic program of remote connectivity...

..This marks a striking difference from similar studies, in which dying oligodendrocytes failed to recruit cells of the adaptive immune system...

..This novel model of a demyelinating neuropathy demonstrates that peroxisomes serve an important function in the peripheral myelin compartment, required for long-term axonal integrity...

..The combined use of a genetic label with laser-microdissection offers an unbiased approach to map patterns of gene expression onto practically any cell type of the brain...

..We suggest that regions of non-compact myelin are under lifelong protection by PTEN against abnormal membrane outgrowth, and that dysregulated phosphoinositide levels play a critical role in the pathology of tomaculous neuropathies...

..Furthermore, ascorbic acid treatment reduced premature death and demyelination in a CMT1A mouse model. Thus, basic research has opened up new vistas for the understanding and treatment of hereditary neuropathies...

..Reduction of SK3 function may constitute a pharmacological target to improve cognition in schizophrenia and other conditions with cognitive impairment...

..We conclude that a Nedd4-1/Rap2A/TNIK signaling pathway regulates neurite growth and arborization in mammalian neurons...

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..Because normal SIRT2 activity is controlled by the NAD+/NADH ratio, its function may be coupled to the axo-glial metabolism and the long-term support of axons by oligodendrocytes...

..Understanding the cross talk between neurons and Schwann cells will help to further define the role of glia in preserving axonal integrity and to develop therapeutic strategies for peripheral neuropathies such as CMT1A...

..We conclude that an important determinant in the quality control of polytopic membrane proteins is the free alignment of their TM domains...

..This review highlights how animal models of demyelinating CMT have improved our understanding of disease mechanisms. Transgenic CMT models also allow therapies to be developed in a preclinical setting...

..However, the contribution of neurons and glial cells to total brain cholesterol metabolism is unknown...

..The GRAS Data Collection as a prerequisite for PGAS has enabled us to associate protective NRG1 genotypes with later onset and milder course of schizophrenia...

..We conclude that peroxisomes provide oligodendrocytes with an essential neuroprotective function against axon degeneration and neuroinflammation, which is relevant for human demyelinating diseases...

..These results illustrate how the integration of unbiased proteome, transcriptome, and genome data can contribute to a molecular dissection of the biogenesis, cell biology, metabolism, and pathology of myelin...

..We suggest that loss of electrostatic cell-surface repulsion uncovers weak and unspecific attractive forces in the bilayer that bring the extracellular surfaces of a membrane into close contact over long distances...

..Thus, BACE1 is not essential for the activation of NRG1 type III to promote myelination. Taken together, these findings suggest that multiple neuronal proteases collectively regulate NRG1 processing...

..These results suggest that hippocampal cGKI supports an age- and protein synthesis-dependent form of hippocampal LTP, whereas it is dispensable for hippocampus-dependent spatial reference and contextual memory...

..This effect is not only inhibited by EPO but also by neurotrophins. We suggest that the proapoptotic function of TPO helps to select for neurons that have acquired target-derived neurotrophic support...

..In Schwann cells of the PNS, protein trafficking and myelin compaction depend on cholesterol. In this review, the authors summarize the role of cholesterol in myelin biogenesis and myelin disease...

..This short review focuses on the possible primary role of oligodendrocytes in axon loss and inflammatory demyelination...

..This interaction of genetic and environmental factors may be relevant for neuropsychiatric diseases associated with secondary neuroinflammation...

..However, M6B is not efficiently sorted into mature myelin, in which it is 200-fold less abundant than PLP. Thus, only PLP contributes to the high cholesterol content of myelin by association and co-transport...

..Analogously, in man, diffusion tensor imaging points to axonal loss in the frontal corpus callosum. To conclude, subtle white matter abnormalities inducing neurodegenerative changes can cause/amplify psychiatric diseases...

..The NEX-Cre mouse will be a valuable tool for behavioral research and the conditional inactivation of target genes in pyramidal neurons of the dorsal telencephalon...

..Thus, NRG1/ErbB signaling is markedly different between Schwann cells and oligodendrocytes that have evolved an NRG/ErbB-independent mechanism of myelination control...

..We suggest that the molecular shift from P0 to PLP also correlates with the concentration of adhesive forces at the radial component, and that the new balance between membrane adhesion and dynamics was favorable for CNS myelination...

..This demonstrates that high-level cholesterol coordinates P0 export with myelin membrane synthesis, which is required for the correct stoichiometry of myelin components and for myelin compaction...

..Thus, covalent protein cross-links emerge as a cause, rather than as a consequence, of endoplasmic reticulum retention...

..This case suggests that rapid cycling is a systemic disease, resembling hibernation, with prostaglandins playing a mediator role...

..These data establish a critical role for mTOR signaling in both the longitudinal and radial growth of the myelinating Schwann cell...

..There were no adverse events, no safety concerns and a surprisingly low need of blood-lettings. This first pilot study demonstrates the necessity and feasibility of controlled trials using high-dose rhEPO in chronic progressive MS...

..This approach is different from and complementary to the genome-wide association studies (GWAS) on schizophrenia...

..Together, these results establish that PIP2 is an essential determinant for stable membrane binding of MBP and provide a novel link between glial phosphoinositol metabolism and MBP function in development and disease...

..Finally single fiber diffraction in highly focused hard X-ray beams, and soft X-ray microscopy and tomography in absorption contrast are demonstrated as novel techniques for the study of single nerve fibers...

..However, the molecular mechanisms leading to the disintegration of tissue-specific clocks are complex and not well understood...

..Taken together, these data provide proof of principle that the progesterone receptor of myelin-forming Schwann cells is a promising pharmacological target for therapy of CMT-1A...

..This combination of preclinical effectiveness and proven safety in humans suggests that high-dose melatonin is suitable for clinical trials aimed at neuroprotection through antioxidation in ALS...

..Shut-off, in contrast, exhibited delayed kinetics, which probably correlated with doxycycline clearance rates. This mouse provides a useful tool for generating tetracycline-controlled gene expression in neural crest and oligodendrocytes...

..These findings provide strong evidence that a primary glial damage can cause secondary immune reactions of pathological significance as it has been suggested for some forms of multiple sclerosis and other leukodystrophies...

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..Whereas UPR-induced cell death governs the PMD phenotype of the msd mutation, we propose that impaired cholesterol and lipid raft interaction of the rsh protein may contribute to the dysmyelination observed in SPG-2...

..These findings may have substantial impact on treatment strategies for leukodystrophic disorders and some forms of multiple sclerosis...

..However, the presence of a molecular and functional damage of the axons suggests that this may be the correct moment to start neuroprotective therapies...

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..Metabolic tracer experiments showed this was not the case. We conclude that PLP(null) myelin is physically less stable and/or less dense than wt myelin...

..These observations corroborate the view that impaired cell surface expression of mutated variants of L1 is a potential explanation for the high number of severe pathogenic mutations identified within the human L1 gene...

..These data also provide a fundamental basis for developing strategies with the potential to target IGF-IGF1R signaling pathways in oligodendrocyte lineage cells for the treatment of demyelinating disorders...

..These findings establish a widespread function of Notch1 in the late steps of mammalian OPC development in vivo...

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..We propose that these accumulations perturb the process of myelination and impair the viability of oligodendrocytes...

..Thus, cyclin D1 expression and its subcellular localization correlate directly with distinct physiological states of Schwann cells in this animal model of CMT1A...

..The direct endocannabinoid-mediated control of hippocampal glutamatergic neurotransmission may constitute a promising therapeutic target for the treatment of disorders associated with excessive excitatory neuronal activity...

..These findings demonstrate the vital relationship between axon defasciculation and Schwann cell number and show the importance of FAK in regulating cell proliferation in the developing nervous system...

..We conclude that, although beta1-integrin may still contribute to other aspects of oligodendrocyte biology, it is not essential for myelination and remyelination in the CNS...

..In addition, we show that glial cells forming at E13.5 arise from a new pool of neuroepithelial progenitors distinct from neuronal progenitors cells, which lends support to the segregating model...

..Thus syntenin plays a role in the migration of oligodendroglial precursors, and we suggest that NG2-syntenin-1 interactions contribute to this...

..We conclude that beta1 integrins in radial glia are required for the proper development of the cerebral cortex, whereas beta1 integrins in migrating neurons are not essential for glial-guided migration and reelin signaling...

..Comparing protein sequences and gene structures from birds, teleosts, one urochordate species, and four invertebrates, we have reconstructed major steps in the evolution of proteolipids...

..The release of myelin membrane from LEs/Ls by neuronal signals may represent a mechanism to control myelin membrane growth...

..As axonal damage may occur after just 3 months and tissue cultures represent a strictly controlled environment, this model may be ideal for testing neuroprotective therapies...

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..Our data suggest that NEX-positive progenitors within the SVZ are committed to a glutamatergic neuronal fate and have evolved to expand the number of cortical output neurons that is characteristic for the mammalian forebrain...

..We suggest that CNP is a glial protein required for maintaining the integrity of paranodes and that disrupted axoglial signaling at this site underlies progressive axonal degeneration, observed later in the CNS of Cnp1-null mice...

..Our results indicate that although cdc42 is required for normal Schwann cell proliferation, rac1 regulates Schwann cell process extension and stabilization, allowing efficient radial sorting of axon bundles...

..These data support the hypothesis that the P0-PLP shift during vertebrate evolution provided a vital neuroprotective function to myelin-forming CNS glia...

..AMPA receptor complex in glial-neuronal recognition and signaling...

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..Thus, we conclude that palmitoylation is a sorting determinant for transport to the myelin membrane...

..0%) developed into adults. These findings demonstrate that some of the nuclei of differentiated neurons in the cerebral cortex of juvenile mice maintain developmental pluripotency...

..2 channel-mediated Ca2+ influx to either process...

..These observations identify LMO4 as a calcium-dependent transactivator that plays a key role in patterning thalamocortical connections during development...