• A functional role for intra-axonal protein synthesis during axonal regeneration from adult sensory neurons. (uiowa.edu)
  • Some researchers have suggested that local, intra-axonal protein synthesis is the answer to this problem. (mblwhoilibrary.org)
  • ALS/FTD-Linked Mutation in FUS Suppresses Intra-axonal Protein Synthesis and Drives Disease Without Nuclear Loss-of-Function of FUS. (ucsd.edu)
  • In this paper, we examine Neu3 sialidase action on axonal gangliosides and resultant axon regeneration, and we assess whether these mechanisms help to explain the different regeneration capacities of CNS and PNS axons. (jneurosci.org)
  • Hao Y, Frey E, Yoon C, Wong H, Nestorovski D, Holzman LB, Giger RJ, DiAntonio A, Collins CA. An evolutionarily conserved mechanism for cAMP elicited axonal regeneration involves direct activation of the dual leucine zipper kinase DLK. (case.edu)
  • Methylcobalamine enhances protein synthesis in nerve cells, and promotes myelinization and axonal regeneration, thus improving nerve health. (netmeds.com)
  • Previous research has established that, when a peripheral neuron's axon is severed, it decreases its synthesis of a number of proteins involved in neurotransmission and increases its synthesis of other proteins involved in regeneration. (case.edu)
  • Blackmore M , Letourneau P. L1, beta1 integrin, and cadherins mediate axonal regeneration in the embryonic spinal cord. (umn.edu)
  • Changes within maturing neurons limit axonal regeneration in the developing spinal cord. (umn.edu)
  • Mislocalization of the predominantly nuclear RNA/DNA binding protein, TDP-43, occurs in motor neurons of ~95% of amyotrophic lateral sclerosis (ALS) patients, but the contribution of axonal TDP-43 to this neurodegenerative disease is unclear. (ox.ac.uk)
  • We applied this approach in primary rat hippocampal neurons to test how local positioning of recycling endosomes contributes to axon outgrowth and found that dynein-driven removal of endosomes from axonal growth cones reversibly suppressed axon growth, whereas kinesin-driven endosome enrichment enhanced growth. (nature.com)
  • Ultimately, we want to understand the role local protein synthesis plays in biological systems such as neurons," said Schuman. (uga.edu)
  • Protein targeting to specific subcellular compartments is a shared feature of cells, but neurons take the challenge to its apogee. (ru.nl)
  • 1971-72 - Cell separation of neurons and glial cells and their ability to synthesise proteins in the rat brain. (pierogiorgi.org)
  • 1985-1988 - Uptake of exogenous proteins by neurons. (pierogiorgi.org)
  • However, the mechanisms by which the expression of Wnt proteins is regulated in neurons are unclear. (biomedcentral.com)
  • Currently, we are focusing on the molecules and cells involved in altering neuronal gene expression in response to axonal injury and in changing the intrinsic growth capacity of these neurons. (case.edu)
  • Strikingly, changes in these peptides occur in two other types of peripheral neurons after axonal injury, namely, sensory and motor neurons. (case.edu)
  • Such localized regulation may be of particular importance in highly polarized cells such as neurons, where the requirement for a specific protein can be at a site far distant from the nucleus. (iucc.ac.il)
  • Here, we summarize recent findings in genetically engineered mouse models that support a role for local translation in axonal expression of -actin and importin 1 in injured adult sensory neurons in vivo. (iucc.ac.il)
  • This massive process of neuronal death has been ascribed mainly to the interruption of a trophic factor supply from target structures rather than to the axonal damage per se. (nih.gov)
  • These result in imbalances in the connectivity of neuronal circuitry, and also negatively impact the intracellular connectivity of neuronal proteins and protein pathways, contributing to cognitive decline associated with AD 6 . (nature.com)
  • Here we report a class of mRNA granules in human neuronal processes that are enriched in the nuclear cap-binding protein complex (CBC) and exon junction complex (EJC) core components, Y14 and eIF4AIII. (frontiersin.org)
  • The existence of mRNAs retaining both nuclear cap binding protein and EJC in the distal sites of neuronal processes suggests that some localized mRNAs have not yet undergone the "very first translation," which contribute to the spatio-temporal regulation of gene expression. (frontiersin.org)
  • Axonal hyperexcitability may represent an adaptive mechanism to overcome conduction failure after peripheral injury, but also displays key features shared with cellular analogues of memory including: site-specific changes in neuronal function, dependence on transient, focal depolarization for induction, and requirement for synthesis of new proteins for expression of long-lasting effects. (tmc.edu)
  • 1-3 While the pathogenesis of ALS is not completely understood, it is thought to involve neuronal damage triggered by protein misfolding, oxidative stress, mitochondrial dysfunction, RNA-processing impairment, neurofilament aggregation, loss of axonal transport, disruption of the neuromuscular junction, and axon demyelination. (uspharmacist.com)
  • Protein aggregates of TDP43 have been found in the neuronal cytoplasm of 97% of ALS patients. (uspharmacist.com)
  • Energy producing metabolism and the synthesis of the macromolecules used by the cell to maintain its structure and execute its function are the principal activities of the neuronal soma. (comoficar.com)
  • In the late 1960s, neurophysiologic testing allowed the classification of CMT into 2 groups, one with slow nerve conduction velocities and histologic features of a hypertrophic demyelinating neuropathy (hereditary motor and sensory neuropathy type 1 or CMT1) and another with relatively normal velocities and axonal and neuronal degeneration (hereditary motor and sensory neuropathy type 2 or CMT2). (medscape.com)
  • Axonal TDP-43 condensates drive neuromuscular junction disruption through inhibition of local synthesis of nuclear encoded mitochondrial proteins. (ox.ac.uk)
  • Specifically, the axonal and synaptic levels of nuclear-encoded mitochondrial proteins are reduced. (ox.ac.uk)
  • TSPO is a ubiquitous mitochondrial protein and is involved in numerous biological functions. (uni-regensburg.de)
  • Nuclear-encoded mitochondrial ribosomal proteins are required to initiate gastrulation[J]. Development, 2020, 147: dev188714. (magtechjournal.com)
  • Alterations in mitochondrial dynamics due to mutations in proteins involved in the fusion-fission machinery represent an important pathogenic mechanism of human diseases. (centrodinoferrari.com)
  • The most relevant proteins involved in the mitochondrial fusion process are three GTPase dynamin-like proteins: mitofusin 1 (MFN1) and 2 (MFN2), located in the outer mitochondrial membrane, and optic atrophy protein 1 (OPA1), in the inner membrane. (centrodinoferrari.com)
  • Dynamin-related protein 1 (DRP1), a cytosolic dynamin-related GTPase, plays a central role in fission by promoting mitochondrial division through its oligomerization into multimeric spiral structures [5]. (centrodinoferrari.com)
  • the lack of correlation between the toxicant-induced changes in axonal transport and mitochondrial ATP production demonstrate the necessity to evaluate other structures as the critical site of action in producing axonal transport changes. (cdc.gov)
  • Xiong X, Wang X, Ewanek R, Bhat P, Diantonio A, Collins CA. Protein turnover of the Wallenda/DLK kinase regulates a retrograde response to axonal injury. (case.edu)
  • 1977-80 - Metabolism of myelin proteins in the rabbit optic pathway. (pierogiorgi.org)
  • While macrophage accumulation in the distal stump of a transected peripheral nerve plays an important role in phagocytosing myelin and axonal debris, their role within peripheral ganglia is unknown and this question is an important part of our current research focus. (case.edu)
  • Through mechanisms that at present can only be speculated about, myelin disturbances result in axonal damage. (medscape.com)
  • Myelinating Schwann cells form a myelin sheath around a single axon and express high levels of myelin-related proteins and messenger RNA (mRNA). (medscape.com)
  • These compounds are involved in nucleic acid metabolism, methyl transfer, and myelin synthesis and repair. (msdmanuals.com)
  • In axons, TDP-43 is hyper-phosphorylated and promotes G3BP1-positive ribonucleoprotein (RNP) condensate assembly, consequently inhibiting local protein synthesis in distal axons and NMJs. (ox.ac.uk)
  • Clearance of axonal TDP-43 or dissociation of G3BP1 condensates restored local translation and resolved TDP-43-derived toxicity in both axons and NMJs. (ox.ac.uk)
  • These data indicate that the glycolytic pathway is operative in distal axons and contributes to the rate of axon extension and growth cone dynamics in the presence of NGF and that, in the absence of NGF, the axonal glycolytic pathway is required for axon maintenance. (jneurosci.org)
  • Axons are therefore vulnerable to stressors that impair energy metabolism, cytoskeleton, axonal transport machinery and glial support as well as acute physical injury. (case.edu)
  • These include cell autonomous signaling pathways that become triggered in damaged axons, and neuron-glial interactions that mediate circuit adaptations to axonal damage. (case.edu)
  • Hao Y, Waller TJ, Nye DM, Li J, Yang Y, Hume RI, Rolls MM, Collins CA. Degeneration of Injured axons and dendrites requires restraint of a protective JNK signaling pathway by the transmembrane protein Raw. (case.edu)
  • Though axons have previously been considered simple conducting cables, spontaneous afferent signals develop from some neuromas that form at severed nerve tips, indicating intrinsic changes in sensory axonal excitability may contribute to this intractable pain. (tmc.edu)
  • Many of the components of axoplasm, such as soluble proteins and cytoskeleton, are slowly transported, taking weeks to months to travel the length of axons longer than a few millimeters after being synthesized in the cell body. (mblwhoilibrary.org)
  • Although dendritic and synaptic protein syntheses are well-established phenomena, the apparent paucity of ribosomes in early studies on mature vertebrate axons generated significant skepticism regarding the possibility of protein synthesis within axons. (iucc.ac.il)
  • Blackmore M , Letourneau P. Protein synthesis in distal axons is not required for axon growth in the embryonic spinal cord. (umn.edu)
  • However, even for CMT1 a heated debate has focused on the relative contribution of axonal versus demyelinative damage to the disease manifestations and progression. (medscape.com)
  • To distinguish between these two possibilities, we induced a reversible axonal transport blockade in the developing optic nerve by topical application of a local anesthetic (lidocaine). (nih.gov)
  • The new method, which uses so-called "caged compounds" that can be turned on with light, could lead to more intricate studies of such important but poorly understood processes, such as protein synthesis in nerve synapses. (uga.edu)
  • Here we show that nerve transection, exposure to serotonin, and transient depolarization induce long-lasting sensory axonal hyperexcitability that is localized to the treated nerve segment and requires local translation of new proteins. (tmc.edu)
  • The finding of axonal hyperexcitability after nerve injury sheds new light on the clinical problem of chronic neuropathic pain, and provides more support for the hypothesis that mechanisms of long-term memory storage evolved from primitive adaptive responses to injury. (tmc.edu)
  • 1. Mecobalamin is well transported to nerve cell organelles than cyanocobalamin and plays the role of coenzyme in the synthesis of methionine from homocysteine. (avenzor.ae)
  • 2. Mecobalamin normalizes axonal transport of skeletal protein in sciatic nerve cells. (avenzor.ae)
  • Nerve repair and axonal transport. (lu.se)
  • The mushroom extract has been found to enhance local axonal protein synthesis in rats, which is vital for nerve repair. (guidedbymushrooms.com)
  • Now a large and ever increasing number of genetic subtypes has been described, and major advances in molecular and cellular biology have clarified the understanding of the role of different proteins in the physiology of peripheral nerve conduction in health and in disease. (medscape.com)
  • We present here sensitive, simple and robust methods for detection of tumor necrosis factor (TNF) mRNA and TNF in histological sections and homogenates of brain tissue from mice subjected to focal cerebral ischemia or hippocampal axonal lesioning. (sdu.dk)
  • Our strategy for detection of TNF mRNA and protein provides a solid basis for clarifying the cellular synthesis, regulation and function of TNF in the normal, injured or diseased CNS. (sdu.dk)
  • Degeneration of these cells was completely prevented by inhibiting protein synthesis during lidocaine application. (nih.gov)
  • Axonal degeneration is a prediction of disability. (medscape.com)
  • PKU is a treatable autosomal recessive inherited metabolic disease and is categorized as per the different etiologies into PKU caused by mutations in the PAH gene resulting in decreased or loss of PAH activity and BH4D deficiency caused by a congenital defect of an enzyme in the synthesis or metabolism pathway of the coenzyme of PAH (BH4) [ 8 , 9 ]. (hindawi.com)
  • Asgari Adib E, Smithson LJ, Collins CA. An axonal stress response pathway: degenerative and regenerative signaling by DLK. (case.edu)
  • 1972-74 - Axonal transport of proteins in the rabbit optic pathway. (pierogiorgi.org)
  • Wnt proteins bind to receptors to activate the Wnt/β-catenin canonical pathway and β-catenin-independent non-canonical pathways, which include the planar cell polarity (PCP) pathway and the Wnt/calcium (Ca 2+ ) pathway [ 2 , 23 - 26 ]. (biomedcentral.com)
  • The activation of the PCP pathway stimulates Rho GTPases and c-Jun N-terminal kinase (JNK) to regulate cell morphogenesis and movement [ 29 ], whereas the activation of the Wnt/Ca 2+ pathway causes Ca 2+ to activate protein kinase C (PKC) and calcium/calmodulin dependent protein kinase II (CaMKII) [ 30 ]. (biomedcentral.com)
  • These proteins take part in the fusion pathway in two consecutive steps. (centrodinoferrari.com)
  • Lysosomes of leukocytes and fibroblasts, dense bodies of platelets, azurophilic granules of neutrophils, and melanosomes of melanocytes are generally larger in size and irregular in morphology, indicating that a common pathway in the synthesis of organelles responsible for storage is affected in patients with CHS. (medscape.com)
  • Through this interaction, mRNAs and their associative proteins form messenger ribonucleoprotein particles (mRNPs) that are actively transported along the cytoskeleton to intracellular destinations. (frontiersin.org)
  • The interior of the soma consists of cytoplasm, a gel within a microtrabecular lattice formed by the microtubules and associated proteins that make up the cytoskeleton . (comoficar.com)
  • These definitive confirmations of mammalian axonal protein synthesis in both transgenic and subcellular knockout models should direct further attention to the diverse roles suggested for local protein synthesis in axonal physiology. (iucc.ac.il)
  • Considering filament polymerization requires ATP, inhibition of glycolysis results in a paradoxical increase in axonal actin filament levels. (jneurosci.org)
  • The new chromophore, called Bhc, is the only one sensitive enough to light that it can mediate light-induced protein synthesis inhibition in a living system. (uga.edu)
  • HSP90 inhibition may also enhance synaptic protein expression via activation of heat shock factor 1 (HSF-1) transcriptional regulation 16 . (nature.com)
  • How does protein synthesis regulate synaptic strength and axonal outgrowth? (uga.edu)
  • Here, we show that Down syndrome critical region 1 protein (DSCR1) controls axon outgrowth by modulating growth cone actin dynamics through regulation of cofilin activity (phospho/dephospho-cofilin). (animabiotech.com)
  • In addition, mitogen-activated protein kinase (MAPK) but not mammalian target of rapamycin (mTOR) inhibitors abolished this Wnt5a synthesis. (biomedcentral.com)
  • This basic two-step process has been confirmed in most mammalian cells, although its regulation and the repertoire of specific accessory proteins are likely to be highly context dependent. (centrodinoferrari.com)
  • We also assessed the development of obesity-induced inflammation by measuring hippocampal level of TNF-alpha, and the extent of protein oxidation by titrating nitro-tyrosine (N-Tyr). (cirn-na.com)
  • If we had a way to selectively abolish protein synthesis in subcellular compartments and observe the effects, then we could infer the role of local protein synthesis in development," said Dore. (uga.edu)
  • Heterogeneous population of RNA granules serve as motile units to translocate, store, translate, and degrade mRNAs in the dendrites contain cis -elements and trans -acting factors such as RNA-binding proteins and microRNAs to convey stimulus-, transcript-specific local translation. (frontiersin.org)
  • Recently I have demonstrated that local production of proteins is a shared feature of both side of the synapses 4 . (ru.nl)
  • Maintenance of functional connectivity requires robust mechanisms for transporting proteins and organelles, in addition to mechanisms for local synthesis of proteins distant from the cell body. (case.edu)
  • It has become increasingly clear that axon extension requires proper actin polymerization dynamics, whereas growth cone steering involves local protein synthesis. (animabiotech.com)
  • Additionally, DSCR1 mediates brain-derived neurotrophic factor-induced local protein synthesis and growth cone turning. (animabiotech.com)
  • Our study identifies DSCR1 as a key protein that couples axon growth and pathfinding by dually regulating actin dynamics and local protein synthesis. (animabiotech.com)
  • 1968-70 - Regulation of nucleic acid and protein synthesis by polyamines in the vertebrate brain. (pierogiorgi.org)
  • It is also involved in the synthesis of thymidine from deoxy uridine thus promoting nucleic acid protein synthesis. (avenzor.ae)
  • 5. Mecobalamin promotes nucleic acid synthesis in the bone marrow and promotes the maturation and division of erythroblasts thereby improving anemia, thus increasing erythrocyte production. (avenzor.ae)
  • The axonal and dendritic patterns of each neurone will be then analysed at high magnification and reconstructed. (europa.eu)
  • We found that axonal transport blockade induced only a limited number of pyknotic RGCs. (nih.gov)
  • Here we establish optical control of intracellular transport by using light-sensitive heterodimerization to recruit specific cytoskeletal motor proteins (kinesin, dynein or myosin) to selected cargoes. (nature.com)
  • Chédiak-Higashi syndrome (CHS) is an autosomal recessive immunodeficiency disorder characterized by abnormal intracellular protein transport. (medscape.com)
  • Whether the neuropathy is caused by reductions in axonal transport produced by energy depletion is under investigation. (cdc.gov)
  • Axonal ribosomes and mRNAs associate with fragile X granules in adult rodent and human brains. (uiowa.edu)
  • Now, a team of chemists and neurobiologists led by Timothy Dore at the University of Georgia and Erin M. Schuman at the California Institute of Technology has found a way to use light to regulate protein synthesis in specific locations. (uga.edu)
  • For this purpose, a transgenic mouse line expressing a green fluorecescent protein (GFP) under the control of the GAD65 (GAD: glutamate decarboxilase enzyme involved in the synthesis of GABA) promoter will be used. (europa.eu)
  • Our lab uses both Drosophila melanogaster and mice as model organisms, when enables us to combine molecular genetics approaches with cell biology, biochemistry and primary cell culture to study conserved pathways of axonal damage response. (case.edu)
  • Recessive ADPRHL2/ARH3 mutations are described to cause a stress-induced epileptic ataxia syndrome with developmental delay and axonal neuropathy (CONDSIAS). (ox.ac.uk)
  • Here, we present two families with a neuropathy predominant disorder and homozygous mutations in ADPRHL2 We characterized a novel C26F mutation, demonstrating protein instability and reduced protein function. (ox.ac.uk)
  • Both the axonal type and the demyelinating type of peripheral neuropathy associated with CHS have been reported. (medscape.com)
  • This suggests that, in most cases, axonal damage is the root cause of the neuropathy, not demyelination. (medscape.com)
  • Tonusin S, Malasao R, Mizuguchi M, et axonal motor neuropathy and mod- al. (cdc.gov)
  • Pertinent to AD pathophysiology, heat shock protein 90 (HSP90)/co-chaperone complex folds tau or hyperphosphorylated tau, whereas heat shock protein 70-carboxyl-terminus of HSP70 Interacting protein (HSP70-CHIP) complex mediates degradation 13 , 14 . (nature.com)
  • Studying protein synthesis in presynaptic terminals will advance our basic understanding of synaptic function and plasticity and will provide critical insights into the early mechanisms underlying NDs. (ru.nl)
  • Live cell imaging and immunolabeling for microtubules and the centralspindlin constituent and kinesin-related protein, MKLP1, demonstrated that furrowing in ammonia-activated eggs was associated with aligned arrays of centralspindlin-linked, opposed bundles of antiparallel microtubules. (mblwhoilibrary.org)
  • This NMDAR-regulated Wnt5a protein increase was blocked by translational but not transcriptional inhibitors. (biomedcentral.com)
  • Immunoreactivity for neurotransmitter receptors, calcium binding proteins and neuropeptides will be visualized by immunocytochemistry and the sections will be processed. (europa.eu)
  • Using cortical primary cultures, we show here that activation of NMDA receptors (NMDARs) induces rapid Wnt5a protein synthesis and secretion. (biomedcentral.com)
  • Another example of a process the new method can help clarify involves the role of protein synthesis in the development of an organism. (uga.edu)
  • We introduce the term protein connectivity-based dysfunction (PCBD) to define this mechanism. (nature.com)
  • We report here a mechanism that couples NMDAR activation to Wnt5a protein synthesis in primary cortical cultures. (biomedcentral.com)
  • This NMDAR-regulated Wnt5a synthesis does not require transcription and is a result of activity-dependent translation. (biomedcentral.com)
  • On the other hand, axonal damage can result in secondary demyelination. (medscape.com)
  • These findings support an axonal gain of function of TDP-43 in ALS, which can be targeted for therapeutic development. (ox.ac.uk)
  • In contrast to the detailed understanding of the intracellular signaling cascades initiated by Wnts, little is known about the upstream mechanisms that control the synthesis of Wnt proteins. (biomedcentral.com)
  • Both types of lesions are characterized by induction of TNF synthesis in resident microglial cells, which in the ischemic lesions are supplemented by TNF synthesizing, blood-borne macrophages. (sdu.dk)
  • Precisely measured protein lifetimes in the mouse brain reveal differences across tissues and subcellular fractions. (ru.nl)
  • Isolated rat brain mitochondria incubated for 30 min at 37 degrees C with neurotoxic doses of ACR (0.7 mM) or 3,4-dimethyl-2,5-hexanedione (0.25 mM) retained similar capacities for synthesis of ATP from pyruvate and endogenous concentrations of ATP compared to controls. (cdc.gov)
  • The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the protein (Fig 5C, residues in blue). (josephineknight.com)
  • Traditionally, CMT pathophysiology has been categorized into 2 processes: a predominant demyelinating process resulting in low conduction velocities (CMT1) and a predominant axonal process resulting in low potential amplitudes (CMT2). (medscape.com)
  • Haptoglobin (Hpt) is an acute phase protein, which acts as antioxidant by binding free haemoglobin (Hb), thus neutralizing its pro-oxidative action. (cirn-na.com)
  • 0.01), inflammation and protein oxidative modification, as evidenced by the increase in the concentration of TNF-alpha and nitro-tyrosine. (cirn-na.com)