• mRNA
  • Exposure of dopaminergic-like cell line to Ibogaine HCl results in an increase in GDNF mRNA, leading to protein expression and to the corresponding activation of the GDNF signaling pathway. (wikipedia.org)
  • The protein encoded by this gene is a member of a family of RNA-binding proteins, has three RNA recognition motifs (RRMs), and binds adenine and uridine-rich elements in mRNA and pre-mRNAs of a wide range of genes. (wikipedia.org)
  • These proteins are associated with pre-mRNAs in the nucleus and appear to influence pre-mRNA processing and other aspects of mRNA metabolism and transport. (wikipedia.org)
  • This mechanism is thought to be more efficient, resulting in an approximately 80% to 95% decrease in the protein and mRNA expression. (wikipedia.org)
  • traumatic brain injury i
  • Study on Cognition Disorder and Morphologic Change of Neurons in Hippocampus Area Following Traumatic Brain Injury in Rats Chinese Journal of Traumatology = Zhonghua Chuang Shang Za Zhi. (jove.com)
  • axon
  • At the same time, developing neurons send out axon outgrowths that contact their target cells. (wikipedia.org)
  • This movement of NGF from axon tip to soma is thought to be involved in the long-distance signaling of neurons. (wikipedia.org)
  • This creates a challenge for supplying new proteins to axon endings that can be a meter or more away from the soma. (wikipedia.org)
  • A current theory of how such survival signals are sent from axon endings to the soma includes the idea that NGF receptors are endocytosed from the surface of axon tips and that such endocytotic vesicles are transported up the axon. (wikipedia.org)
  • mutations
  • Of the familial cases, ~4% are due to mutations in TARDBP , encoding TAR DNA Binding Protein (TDP-43) [ 2 , 3 ]. (molecularneurodegeneration.com)
  • Interestingly, a proportion of sporadic ALS cases have also been attributed to TDP-43 mutations [ 2 , 3 ]. (molecularneurodegeneration.com)
  • Mutations in the SOD1 gene only account for about 2 percent of all ALS cases, but the discovery of the mutations in 1993 was a breakthrough for scientists trying to get a handle on the disease. (alzforum.org)
  • Since then, over 100 SOD1 mutations have been linked to inherited familial ALS (fALS) and while all the mutated proteins seem to form large protein aggregates, exactly how these aggregates tie in with pathology has been debated. (alzforum.org)
  • Wang and colleagues found that together, protein aggregation and protein instability account for 69 percent of the variation in survival associated with different SOD1 mutations. (alzforum.org)
  • Pubmed ID: 29086942 X-linked Charcot-Marie-Tooth disease is caused by mutations in the gene for the gap junction protein connexin32. (jove.com)
  • gene
  • SMA is caused by mutation of the survival motor neuron (SMN) gene. (nii.ac.jp)
  • We defined 0-2 copies/ 2 chromosomes as a deletion of he H4F5 gene. (nii.ac.jp)
  • Neuritin 1 is a protein that in humans is encoded by the NRN1 gene. (wikipedia.org)
  • The protein encoded by this gene is a nuclear protein that has been identified as a constituent of the spliceosome complex. (nih.gov)
  • TDP-43 (encoded by TARDBP ) is an ALS-causative gene that we have previously implicated in the regulation of the core stress granule proteins G3BP and TIA-1. (molecularneurodegeneration.com)
  • Glial cell-derived neurotrophic factor (GDNF) is a protein that, in humans, is encoded by the GDNF gene. (wikipedia.org)
  • Here we reveal that SMN is a chromatin-binding protein that specifically interacts with methylated histone H3K79, a gene expression- and splicing-associated histone modification. (embl-heidelberg.de)
  • Nucleolysin TIAR is a protein that in humans is encoded by the TIAL1 gene. (wikipedia.org)
  • Heterogeneous nuclear ribonucleoprotein U is a protein that in humans is encoded by the HNRNPU gene. (wikipedia.org)
  • The protein encoded by this gene contains a RNA binding domain and scaffold-associated region (SAR)-specific bipartite DNA-binding domain. (wikipedia.org)
  • So CCDS's gene number prediction represents a lower bound on the total number of human protein-coding genes. (wikipedia.org)
  • The term epigenetics refers to three levels of gene regulation: (1) DNA methylation, (2) histone modifications, and (3) non-coding RNA (ncRNA) function. (wikipedia.org)
  • Brain-derived neurotrophic factor, also known as BDNF, is a protein that, in humans, is encoded by the BDNF gene. (wikipedia.org)
  • The BDNF protein is encoded by a gene that is also called BDNF, found in humans on chromosome 11. (wikipedia.org)
  • The protein encoded by this gene is a dimeric enzyme that catalyzes the reversible isomerization of G6P and F6P. (wikipedia.org)
  • Bcl-2-like protein 2 is a protein that in humans is encoded by the BCL2L2 gene. (wikipedia.org)
  • Studies of the related gene in mice indicated a role in the survival of NGF- and BDNF-dependent neurons. (wikipedia.org)
  • Leucine rich repeat and Immunoglobin-like domain-containing protein 1 also known as LINGO-1 is a protein which is encoded by the LINGO1 gene in humans. (wikipedia.org)
  • mitochondrial
  • Some theories suggest that it is not aggregation of the protein that causes disease, but aberrant activity (see ARF related news story ) or downstream effects such as mitochondrial-induced apoptosis (see ARF related news story ). (alzforum.org)
  • Ro5-4864 was found to be a potent ligand for the "peripheral benzodiazepine receptor", later renamed to mitochondrial translocator protein 18kDa (TSPO). (wikipedia.org)
  • kinase
  • Within 15 to 30 min after HNE treatment, c-Jun N-terminal protein kinase (JNK) was maximally activated, before it returned to control level at 1 h post-treatment. (aspetjournals.org)
  • Stress-activated protein kinase kinase (SEK1), an upstream kinase of JNK, was also activated within 5 min after HNE treatment and remained activated for up to 60 min. (aspetjournals.org)
  • Marked activation of the JNK pathway through SEK1 and apoptosis signal-regulating kinase 1 (ASK1), an upstream kinase of SEK1, was demonstrated by the transient transfection of cDNA for wild-type SEK1 or ASK1 together with JNK into COS-7 cells. (aspetjournals.org)
  • Pretreatment of PC12 cells with SB203580, a specific inhibitor of p38 MAP kinase, had no effect on HNE-induced apoptosis. (aspetjournals.org)
  • All these data suggest that the selective JNK activation by HNE is critical for the apoptosis of PC12 cells and that the HNE-mediated apoptosis is likely to be mediated through the activation of the ASK1-SEK1-JNK pathway without activation of extracellular signal-regulated kinase or p38 MAP kinase. (aspetjournals.org)
  • Nissl stain, acid fuchsin stain and immunohistochemistry with phosphorylated extracellular signal-regulated protein kinase (pERK) antibody were used in order to assess posttraumatic neurons. (springer.com)
  • Alessandrini A, Namura S, Moskowitz MA, Bonventre JV (1999) MEK1 protein kinase inhibition protects against damage resulting from focal cerebral ischemia. (springer.com)
  • Dash PK, Mach SA, Moore AN (2002) The role of extracellular signal-regulated kinase in cognitive and motor deficits following experimental traumatic brain injury. (springer.com)
  • LINGO-1 is involved in the regulation of neural apoptosis by inhibiting WNK3 kinase activity. (wikipedia.org)
  • precursors
  • SMN serves as a chaperone in the assembly of spliceosome precursors by combining small nuclear RNA (snRNA) molecules with Sm proteins to generate small nuclear ribonucleoproteins (snRNPs) [ 22 , 23 ]. (hindawi.com)
  • The last ribozyme motif, the RNase P ribozyme, is found in Escherichia coli and is known for its ability to cleave the phosphodiester bonds of several tRNA precursors when joined to a protein cofactor. (wikipedia.org)
  • apoptotic
  • Overexpression of the anti-apoptotic protein Bcl-2 attenuates neurodegeneration and delays activation of the caspases and fragmentation of β-actin. (jneurosci.org)
  • As illustrated below, mounting evidence indicates that mSOD1-induced spinal cord motor neuron death involves, at least in part, the apoptotic molecular machinery. (jneurosci.org)
  • In the present study, we demonstrate (1) that caspase-1 and caspase-3 are activated sequentially in the spinal cords of affected transgenic mSOD1 mice, (2) that activated caspase-3 is localized within neurons of the anterior horn that exhibit apoptotic features, and (3) that overexpression of Bcl-2 delays caspase activation in these animals. (jneurosci.org)
  • Bcl-2 homology-3 domain (BH3)-only proteins are pro-apoptotic members of the Bcl-2 family whose enhanced expression acts as a trigger for the intrinsic apoptotic cascade. (frontiersin.org)
  • The upregulation of a specific subset of BH3-only proteins, including Bid, DP5/Hrk, and BNip3L, in reactive astrocytes suggests that these proteins may execute a novel non-apoptotic function within astrocytes to promote ALS disease progression, thus providing a new potential target for therapeutic intervention. (frontiersin.org)
  • 4 The elimination of cell debris occurs in the absence of an inflammatory response, and this quiet, rapid, and efficient removal of apoptotic cells means that apoptosis can be difficult to detect in tissue: although as many as 50% of the cells in a developing organ may undergo apoptosis, less than 1% of cells are apoptotic at any one time. (bmj.com)
  • activation domain 2 (AD2) important for apoptotic activity: residues 43-63. (wikipedia.org)
  • The proteins of this family form hetero- or homodimers and act as anti- and pro-apoptotic regulators. (wikipedia.org)
  • developmental
  • Programmed cell death by apoptosis occurs in many developmental processes, including body sculpting (such as digit formation), elimination of self-reacting immune cells, sexual organ development and gamete formation. (bmj.com)
  • Exerts its major developmental effects in somatosensory neurons and in brainstem nuclei involved in motor control. (uniprot.org)
  • genes
  • Tumor protein p53, also known as p53, cellular tumor antigen p53 (UniProt name), phosphoprotein p53, tumor suppressor p53, antigen NY-CO-13, or transformation-related protein 53 (TRP53), is any isoform of a protein encoded by homologous genes in various organisms, such as TP53 (humans) and Trp53 (mice). (wikipedia.org)
  • glial
  • Gradually some of the cells stop dividing and differentiate into neurons and glial cells, which are the main cellular components of the CNS. (wikipedia.org)
  • Research shows that glutamate receptors are present in CNS glial cells as well as neurons. (wikipedia.org)
  • mRNAs
  • Evidence shows that SMN is also involved in the stabilization and maturation of the neuromuscular junction and the transportation of axonal mRNAs in motor neurons [ 25 - 27 ]. (hindawi.com)
  • In general, most proteins are produced from mRNAs that do not travel far from the cell nucleus. (wikipedia.org)
  • neuromuscular
  • On the other hand, inappropriate apoptosis resulting in the removal of healthy cells can occur in diseases such as infection, hypoxic-ischaemic injury, neurodegenerative or neuromuscular diseases, and AIDS. (bmj.com)
  • cellular
  • These lipid peroxides can directly damage cells and tissues through interaction with cellular macromolecules, including proteins, lipids, and nucleic acids. (aspetjournals.org)
  • Dysregulation of apoptosis is seen after cellular insults or in neurodegeneration as well as in tumourigenesis. (bmj.com)
  • In contrast, apoptosis is cellular suicide. (bmj.com)
  • Here, we show fibrillarin domain conservation, structure and interacting molecules in different cellular processes as well as with several viral proteins during virus infection. (embl-heidelberg.de)
  • Despite its abundant use as a household protein, little is known about its exact cellular localization and dynamics. (embl-heidelberg.de)
  • Induces
  • Conti AC, Raghupathi R, Trojanowski JQ, McIntosh TK (1998) Experimental brain injury induces regionally distinct apoptosis during the acute and delayed post-traumatic period. (springer.com)
  • It is hypothesized that serine phosphorylation of this protein induces a conformational change to its secretory form. (wikipedia.org)
  • hippocampal
  • Pubmed ID: 11835755 To explore the correlation between cognition disorder and morphologic change of hippocampal neurons after traumatic brain injury (TBI). (jove.com)
  • autosomal recessive
  • SMA exhibits an autosomal recessive pattern of inheritance with an incidence of 1 in 6,000-10,000 newborns and a carrier frequency of about 1 : 35 [ 2 , 3 ]. (hindawi.com)
  • mice
  • Our study also suggests that modulation of caspase activity may provide protective benefit in the treatment of ALS, a view that is consistent with our recent demonstration of caspase inhibition extending the survival of transgenic mSOD1 mice. (jneurosci.org)
  • Here, we compared the relative expression of BH3-only proteins in the spinal cord of end-stage G93A mutant SOD1 mice to age-matched wild-type (WT) mice. (frontiersin.org)
  • however, no discernible differences were observed in either the relative intensity of staining or number of BH3-immunoreactive motor neurons between WT and mutant SOD1 mice. (frontiersin.org)
  • Levels of reactive oxygen species were increased in motor neurons from ALS mice compared with wild-type mice at age 10 weeks, before symptom onset. (aspetjournals.org)
  • Stem cell transplantation in SMA model mice resulted in improvement of motor behaviors and extension of survival, likely from trophic support. (hindawi.com)
  • Knockout mice also exhibit cerebellar abnormalities and an increase in the number of sympathetic neurons. (wikipedia.org)
  • distinct
  • Two distinct modes of cell death-necrosis and apoptosis-are involved in pathological neuronal loss, but apoptosis alone is the mechanism of programmed cell death during development. (bmj.com)
  • In addition to the transcript encoding GDNF, two additional alternative transcripts encoding distinct proteins, referred to as astrocyte-derived trophic factors, have also been described. (wikipedia.org)
  • The hnRNP proteins have distinct nucleic acid binding properties. (wikipedia.org)
  • The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. (wikipedia.org)
  • binds
  • Chromatin immunoprecipitation confirmed that SMN binds to H3K79me1,2-containing chromatin in iCDR-induced cells. (embl-heidelberg.de)
  • These two proteins are p75 (NTR), which binds to all neurotrophins, and subtypes of Trk, which are each specific for different neurotrophins. (wikipedia.org)
  • NGF is released from the target cells, binds to and activates its high affinity receptor TrkA on the neuron, and is internalized into the responsive neuron. (wikipedia.org)
  • nervous system
  • These two brain structures are responsible for motor functions and linking the nervous system to the endocrine system, respectively. (wikipedia.org)
  • Neurodegenerative diseases are a heterogenous group of complex disorders linked by the degeneration of neurons in either the peripheral nervous system or the central nervous system. (wikipedia.org)
  • See the Motor Neuron Fact Sheet for details regarding other motor neuron diseases.Neurodegenerative diseases of the central nervous system can affect the brain and/or spinal cord. (wikipedia.org)
  • During the development of the vertebrate nervous system, many neurons become redundant (because they have died, failed to connect to target cells, etc.) and are eliminated. (wikipedia.org)
  • They are small proteins that secrete into the nervous system to help keep nerve cells alive. (wikipedia.org)
  • It belongs to the family of leucine-rich repeat proteins which are known for playing key roles in the biology of the central nervous system. (wikipedia.org)
  • synthesis
  • Shh works through a slow protein synthesis dependence, which stimulates other cascades that work synergistically with the PI3K/AKT pathway to induce proliferation. (wikipedia.org)
  • A high amount of protein synthesis occurs in this region, as it contains a large number of Nissl granules (which are ribosomes wrapped in RER) and polyribosomes. (wikipedia.org)
  • molecular
  • In this study, we investigated the molecular mechanism of HNE-induced apoptosis in these cells. (aspetjournals.org)
  • Fibrillarin is an essential protein that is well known as a molecular marker of transcriptionally active RNA polymerase I. Fibrillarin methyltransferase activity is the primary known source of methylation for more than 100 methylated sites involved in the first steps of preribosomal processing and required for structural ribosome stability. (embl-heidelberg.de)
  • occurs
  • Accumulation of mutant polyglutamine-containing proteins occurs in patients, and evidence from cell culture and animal experiments suggests the nucleus as a site of pathogenesis. (jove.com)
  • Cleavage occurs at the SALD site, resulting in a loss of DNA-binding activity and a concomitant detachment of this protein from nuclear structural sites. (wikipedia.org)
  • In mammals, methylation occurs on DNA and histone proteins. (wikipedia.org)
  • DNA methylation occurs on the cytosine of CpG dinucleotides in the genomic sequence, and protein methylation occurs on the amino termini of the core histone proteins - most commonly on lysine residues (Bradley et al. (wikipedia.org)
  • histone
  • The Tudor protein survival motor neuron (SMN) is a chromatin-binding protein that interacts with methylated lysine 79 of histone H3. (embl-heidelberg.de)
  • Panobinostat inhibits multiple histone deacetylase enzymes, a mechanism leading to apoptosis of malignant cells via multiple pathways. (wikipedia.org)
  • At its most repressive state, involving many folds into itself and other scaffolding proteins, DNA-histone structures form constitutive heterochromatin. (wikipedia.org)
  • The most relevant epigenetic modifications to treatment of neurodegenerative diseases are DNA methylation and histone protein modifications via methylation or acetylation. (wikipedia.org)
  • differentiate
  • They belong to a class of growth factors, secreted proteins that are capable of signaling particular cells to survive, differentiate, or grow. (wikipedia.org)
  • The type of growth factor signaling can effect whether or not NSCs differentiate into motor neurons or not. (wikipedia.org)
  • Directly inhibiting PI3K in NSCs leads to a population of cells that are purely HB9+ and differentiate at an elevated efficiency into motor neurons. (wikipedia.org)
  • SOD1
  • Finally, examination of protein expression using western blotting also revealed marked increases in DP5/Hrk and BNip3L in G93A mutant SOD1 lumbar spinal cord lysates compared to WT controls. (frontiersin.org)
  • molecules
  • These catalytic RNA molecules bind to a specific site and attack the neighboring phosphate in the RNA backbone with their 2' oxygen, which acts as a nucleophile, resulting in the formation of cleaved products with a 2'3'-cyclic phosphate and a 5' hydroxyl terminal end. (wikipedia.org)
  • SMN2
  • [ 10 ] SMN2 differs from it by 1 C-T transition in exon 7, leading to alternate splicing and a nonfunctional protein for 70-90% of the protein produced. (medscape.com)
  • onset
  • ALS is a rapidly progressive disorder, typically causing death within 2-5 years of onset ( Pasinelli and Brown, 2006 ). (frontiersin.org)
  • The faster aggregating proteins were associated with shorter survival after disease onset. (alzforum.org)
  • Might proteins that are inherently more unstable and more likely to unfold aggregate faster and cause even more rapid onset? (alzforum.org)