Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alzheimer's disease results in the appearance of cytoskeletal disorders yielding pathological structures such a neurofibrillary tangles or dystrophic neurites. It has been previously described that the microtubule-associated protein, tau, modified by phosphorylation in serines adjacent to prolines, is a major component of these structures. Here, we show that another microtubule associated protein, MAP1B, aberrantly phosphorylated by a proline-dependent protein kinase, is a component of these previously mentioned structures. Thus, a possible common phosphorylation of axonal MAPs such as tau or MAP1B may correlate with their association with those aberrant cytoskeletal structures present in AD.
Brain Res Mol Brain Res 1994 Oct
PMID:Microtubule-associated protein MAP1B showing a fetal phosphorylation pattern is present in sites of neurofibrillary degeneration in brains of Alzheimer's disease patients. 785 37

We cloned genes the expression of which were induced 3 days after cortical injury of rat brain by a differential display technique, and four novel and known sequences were isolated. Among these sequences, the sgk gene which was recently identified as a novel member of the serine/threonine protein kinase gene family, was selected for analysis of its expression patterns in rat brain by northern blotting and in situ hybridization, because hybridization signals were strong at the lesion sites. Expression of sgk mRNA was induced within 3 days after injury, and was maintained at a high level for at least 14 days. The cells which strongly expressed the sgk gene were in the deep layers of the cortex and in the corpus callosum. In situ hybridization analysis for sgk and myelin proteolipid protein mRNA using serial sections showed that the distribution of both signals was very similar at the damaged regions. Therefore, it is likely that the sgk transcript is expressed by oligodendrocytes after brain injury. Investigation of the developmental expression of the sgk gene showed that neurons in layers I and II of the cortex, lateroposterior and laterodorsal thalamic nucleus, and ventral posterolateral and posteromedial thalamic nucleus strongly expressed sgk mRNA at postnatal day 1 and day 7, but these neurons showed no expression in fetal or adult brain. These results suggest that the induction of sgk gene may be associated with a series of axonal regenerations after brain injury, and in addition, the sgk gene may also play important roles in the development of particular groups of neurons in the postnatal brain.
Brain Res Mol Brain Res 1994 Oct
PMID:Differential expression of sgk mRNA, a member of the Ser/Thr protein kinase gene family, in rat brain after CNS injury. 785 47

Distribution and ultrastructural localization of a novel phosphoneuroprotein with a molecular mass of 14 kDa (PNP 14), and expression of its mRNA were studied in the adult rat central nervous system (CNS) by immunocytochemistry and in situ hybridization histochemistry. PNP 14 immunoreactivity was abundant in the molecular layer, present moderately in the granular layer, and rare in the Purkinje cell layer of the cerebellar cortex. No PNP 14 immunoreactivity was detected in the cerebellar medulla. In the forebrain, immunoreactivity was found in the hippocampus, striatum, and throughout the cerebral cortex, especially in layer V. Electron microscopic immunocytochemical observation in the cerebellar cortex revealed many PNP 14-immunoreactive axon terminals making synaptic contact with dendritic processes in both granular and molecular layers. PNP 14 immunoreactivity was present mainly in the cytoplasmic matrix in the presynaptic axon terminals. PNP 14 mRNA was localized in the granular layer of the cerebellar cortex, in the hippocampus, and in the cerebral cortex, suggesting that PNP 14 is synthesized in neurons of the granular layer and then transported to the molecular layer by axonal transport. These morphological findings suggest that PNP 14 is likely to modulate the function of selected CNS synapses.
Brain Res Mol Brain Res 1994 Nov
PMID:Localization of phosphoneuroprotein 14 (PNP 14) and its mRNA expression in rat brain determined by immunocytochemistry and in situ hybridization. 787 58

Biodegradable controlled-release microsphere systems made with the biocompatible biodegradable polyester excipient poly(DL-lactide-co-glycolide) constitute an exciting new technology for drug delivery to the central nervous system (CNS). Implantable controlled-release microspheres containing dopamine (DA) or norepinephrine (NE) provide a novel means to compare DA- or NE -induced restitution of function in unilateral 6-hydroxydopamine lesioned rats. A suspension of 3 microL of DA- or NE-containing microspheres or empty microspheres was implanted in 2 sites of the DA denervated striatum of rats previously unilaterally lesioned with 6-hydroxydopamine. Contralateral-rotational behavior induced by apomorphine was used as an index of lesion success and, following implantation of the microspheres, also as an index of functional recovery. Interestingly, both DA- and NE-microsphere-implanted rats displayed a 30-50% reduction in the number of apomorphine-induced rotations up to 8 wk postimplantation. Rats implanted with empty microspheres did not demonstrate significant changes in contralateral rotational behavior. Behavioral studies following implantation of a mixture of DA and NE microspheres revealed an 80% decrease in the number of apomorphine induced rotations up to 4 wk. On conclusion of the studies, immunocytochemical examination revealed growth of DA and tyrosine hydroxylase immunoreactive fibers in the striatum of DA and NE microsphere-implanted rats. Functional behavior appeared to correlate with the degree of fiber growth. Preliminary electron microscopic studies showed signs of axonal sprouting in the vicinity of the implanted microspheres. No growth was noted in rats implanted with empty microspheres. This report reviews the abilities of both microencapsulated NE and DA to assure functional recovery and to promote DA fiber (re)growth in parkinsonian rats. This novel means to deliver these substances to the central nervous system could be of therapeutic usefulness in Parkinson's disease.
Mol Neurobiol
PMID:Catecholamine-containing biodegradable microsphere implants as a novel approach in the treatment of CNS neurodegenerative disease. A review of experimental studies in DA-lesioned rats. 788 96

Neurochemical observations on cortical biopsies form 48 patients under surgical treatment for pharmacoresistant partial epilepsy showed a 70-80% increase in glutamate concentration when expressed in relation to neuron specific enolase. Intraperitoneal administration of one of its receptor agonists, kainic acid (KA), to the rat led to increased epileptogenic activity of the limbic type in a dose-dependent fashion. The KA injection also led to a neuronal cell death and a gliosis, closely correlated to the extent of seizure activity. In biopsies from human epileptogenic cortex, the concentration of neuron specific enolase correlated inversely to that of glial fibrillary acidic protein, a marker for astrocytic glial cells. Stimulation of the KA receptor decreased the extent of phosphorylation of the largest subunit of neurofilaments (NF-H) that have consequences for structural stability and axonal transport. Phosphorylated NF-H decreased also in human epileptic cortex, indicating either an overactivity of excitatory neurotransmitters or a loss of axonal compartments.
Mol Neurobiol
PMID:Excitotoxicity. Experimental correlates to human epilepsy. 788 4

Trimethyltin (TMT) destroys specific subfields of the hippocampus in the rat. TMT also increases choline acetyltransferase (ChAT) activity in CA1 of Ammon's horn and the outer molecular layer of the dentate gyrus. This observation suggests that axonal sprouting occurs in the cholinergic septohippocampal system in response to TMT. However, neither does-response nor time course data are available for the effects of TMT on this enzyme. The effects of three dose levels of TMT on ChAT activity in CA1 and the dentate gyrus were determined in Experiment 1 and ChAT activity in these two areas was measured at six time points following exposure to TMT in Experiment 2. Only the highest dose of TMT (6 mg/kg) significantly increased ChAT activity. ChAT activity in the dentate gyrus increased significantly by 3 d after administration and continued to increase until 21 d after exposure. A significant increase was not observed in CA1 until 7 d after exposure to TMT. Asymptotic levels were still reached at d 21. These results indicate a steep dose-response curve for TMT-induced changes in ChAT activity in the hippocampal formation and that this marker of cholinergic activity is more sensitive to perturbation by TMT in the dentate gyrus than Ammon's horn.
Mol Chem Neuropathol 1994 Sep
PMID:Effects of trimethyltin (TMT) on choline acetyltransferase activity in the rat hippocampus. Influence of dose and time following exposure. 789 29

Reactive gliosis is part of the response of central nervous system to injury and neurodegeneration. Cellular components of the reactive gliosis have the capability to synthesize neurotrophic factors, and thus are capable of affecting the fate of neuronal populations in the injured tissue. In this study, we explored the putative involvement of reactive glia-derived neurotrophins in sustaining the axonal projections of target-deprived neurons. Neuronal targets of the dorsal column nuclei neurons were suppressed through excitotoxic lesion of the ventrobasal complex of the rat thalamus (VB). Despite the development of reactive gliosis, neither up-regulation of NGF, nor BDNF or NT3 mRNA could be detected by solution hybridization in the lesioned site at all times tested. In contrast, expression of the LNGFR gene increased progressively up to 90 days post-lesion. Immunocytochemical studies localized the LNGFR protein in a subset of small cells with ramified processes resembling microglia at 7 and 20 days post-lesion. At longer times, double immunolabelling studies revealed that a substantial part of LNGFR-immunoreactive cells filling the area of neuronal loss were neither microglial cells nor astrocytes although presence of LNGFR in a subset of microglial cells could not be excluded. Previous ultrastructural studies of the kainate-lesioned VB suggest that these LNGFR-immunoreactive cells correspond to oligodendrocytes and/or Schwann cells. At 2 months post-lesion, when LNGFR expression was maximal, increased levels of trkA mRNA were detected in the lesioned site. Immunocytochemical studies revealed the presence of numerous trkA-immunoreactive astrocytes. TrkB mRNA, encoding the full-length high-affinity receptor for BDNF, remained undetectable by non-isotopic in situ hybridization. In contrast to the lack of neurotrophin gene expression by glial components of the lesioned VB, dorsal column nuclei neurons contained NGF mRNA as revealed by in situ hybridization studies at 10 days--prior to enhanced LNGFR expression in the lesion--and 2 months post-lesion. In addition, the number and the staining intensity of NGF mRNA-positive neurons was increased in the target-deprived neurons, as compared with the contra-lateral nucleus projecting to intact targets. These results show that glial cells present in a reactive gliosis which develops in the kainic acid-lesioned thalamus, do not synthesize neurotrophins but instead produce high levels of both low- and high-affinity NGF receptors, LNGFR by Schwann cells/oligodendrocytes and possibly a subset of microglial cells, and trkA by reactive astrocytes.(ABSTRACT TRUNCATED AT 400 WORDS)
Brain Res Mol Brain Res 1994 Jul
PMID:Target-deprived CNS neurons express the NGF gene while reactive glia around their axonal terminals contain low and high affinity NGF receptors. 796 64

To determine if axotomy-induced immediate early gene (IEG) expression accompanies regenerative efforts in central nervous system (CNS) neurons, immunohistochemistry using antibodies to c-Jun, JunD, JunB, c-Fos, FosB and Krox-24 proteins was used to examine gene expression in identified adult rat retinal ganglion cells (RGCs) under two conditions: (1) after axotomy alone, and (2) 1 month after replacement of the optic nerve with an autologous peripheral nerve graft to allow axonal regrowth. Strong RGC c-Jun expression was induced 1 day, but not 3 h, after axotomy in most RGCs and was maintained in surviving cells throughout the 3-week study period. Axotomy also induced a limited number of RGCs to express Krox-24, but only transiently. c-Fos expression was also seen in a limited number of control RGCs, however, it was not induced by axotomy. Nucleolar FosB immunoreactivity in axotomized RGCs persisted 1 day after axotomy, but was subsequently lost. One month after axotomy and peripheral nerve graft placement, identified RGCs with regrown axons showed only nuclear c-Jun and nucleolar FosB expression. These findings support a role for IEG expression in the regeneration process of CNS neurons.
Brain Res Mol Brain Res 1994 Jul
PMID:Immediate early gene expression in axotomized and regenerating retinal ganglion cells of the adult rat. 796 76

A cell surface glycoprotein has been identified from detergent extracts of cultured astrocytes obtained from neonatal rat cerebral cortex using a mouse monoclonal antibody (MAb 1A1). This antibody inhibits neuron-astrocyte and astrocyte-astrocyte adhesion, as well as neurite outgrowth on astrocytes in vitro. The MAb 1A1 does not bind to tissue sections, but by indirect immunofluorescence of dissociated CNS cultures, the antibody labels subpopulations of astrocytes (flat, type 1 astrocytes and Bergmann glia) and cells derived from the mesenchyme (leptomeninges and fibroblasts). The latter cells are labeled only when grown to confluency. The 1A1 cell surface glycoprotein appears as a single band of approximately 135 kDa on both reduced and nonreduced SDS-PAGE. Based on its unique cell-type distribution, functional properties and biochemical analysis, this 135-kDa protein appears to be distinct from other known adhesion molecules expressed on astrocytes. This molecule, thus, belongs to the growing list of cell adhesion molecules that may play a role in histogenesis and axonal growth during development of the mammalian CNS.
Mol Cell Neurosci 1994 Feb
PMID:A monoclonal antibody that recognizes an adhesion molecule expressed by certain cells of neuroectodermal and mesenchymal origin. 808 15

The question of how the cell surface molecules may be specifically delivered to subdomains of neurons is of particular interest considering that polarized sorting to the axon could enable adhesion glycoproteins to induce fasciculation of axonal tracts, guidance to the target cell, and the establishment of synaptic contacts. It was recently proposed that GPI-anchored molecules undergo preferential delivery to the axonal surface, implicating a similar polarized sorting of glycoproteins in neurons and epithelial cells (Dotti and Simons, 1990; Dotti et al., 1991). This review focuses on the cellular and subcellular localization of several glypiated adhesion molecules (Thy-1, TAG-1, F3/F11, P-31) in the developing and adult cerebellar cortex of the mouse. We conclude that the cellular distribution of GPI-anchored adhesion molecules within neurons is very complex and depends on: 1. The neuronal cell types, for example, F3/F11 is localized in axons in granule cells but is present in all compartments of Golgi cells. 2. The molecule itself: Thy-1, TAG-1, and P-31 are present on the granule cell body, whereas at the same developmental stage, F3/F11 is restricted to the axon. 3. The differentiation state: Thy-1 delivery to the axon correlates with postsynaptic target maturation.
Mol Neurobiol 1993
PMID:Are the glypiated adhesion molecules preferentially targeted to the axonal compartment? 810 Apr 20


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>