• In my laboratory researchers are examining the roles played by axonal cytoskeletal proteins in nervous system development, and in the etiology of Alzheimer's and other related neurodegenerative diseases. (uml.edu)
  • N-hexane neurotoxicity: a mechanism involving pyrrole adduct formation in axonal cytoskeletal protein. (cdc.gov)
  • Literature on the neurotoxic effects of n-hexane (110543) was reviewed, and hypotheses for mechanisms linking pyrrole (109977) formation in axonal cytoskeletal protein with nerve degeneration in gamma-diketone neuropathy were presented. (cdc.gov)
  • Slow axonal transport is the mechanism by which cytoskeletal proteins are distributed within the axon. (jneurosci.org)
  • Previous observations of cytoskeletal redistribution in surviving, transected axons of the C57BL/Ola mouse led us to hypothesize a retrograde component of cytoskeletal transport. (jneurosci.org)
  • Slow axonal transport of cytoskeletal proteins proceeded with the same characteristics in C57BL/Ola as in standard C57BL/6 mice. (jneurosci.org)
  • These observations demonstrate that pulse-labeled cytoskeletal proteins move bidirectionally in this experimental system, and may provide insight into the normal mechanisms of cytoskeletal maintenance. (jneurosci.org)
  • Type III intermediate filament proteins that assemble into neurofilaments, the major cytoskeletal element in nerve axons and dendrites. (bvsalud.org)
  • Types I, II, and IV intermediate filament proteins form other cytoskeletal elements such as keratins and lamins. (bvsalud.org)
  • The aberrant accumulation of cytoskeletal-associated proteins causes neurodegeneration resulting in both motor and sensory dysfunction. (journalmc.org)
  • Cytopathologically, the disorder is characterized by giant axons with derangements of the cytoskeletal components. (journalmc.org)
  • The defect in the gigaxonin system leads to the aberrant accumulation of cytoskeletal-associated proteins (neurofilaments) due to defective function of the ubiquitin-proteasome system (UPS). (journalmc.org)
  • It further sought to examine the role of cytoskeletal proteins, particularly the neurofilament (NF) triplet, in the reaction of axons to injury and subsequent sequence of cellular changes involved in neuropil restoration. (edu.au)
  • Our result is limited to small cargo diffusivity, which is a reasonable assumption for many slow axonal transport cargos (such as cytosolic and cytoskeletal proteins, neurofilaments, actin, and microtubules) which are transported as large multiprotein complexes or polymers. (asme.org)
  • This area is free of ribosomes and most other cell organelles, with the exception of cytoskeletal elements and organelles that are being transported down the axon. (comoficar.com)
  • The present research examines the manifestation of neurofilament weighty (NFH) proteins, a protein frequently indicated within sensory neurons that provide rise to myelinated afferents [12], to check the hypothesis that lots of from the unmyelinated pulpal afferents inside the human being dental care pulp result from myelinated axons. (scienza-under-18.org)
  • To test this hypothesis against previous methods of measuring slow transport of cytoskeleton, we radioactively pulse-labeled proteins in sensory neurons of C57BL/Ola mice and followed their redistribution by gel fluorography in ligated and unligated sciatic nerves. (jneurosci.org)
  • Levels of neurofilament light chain (NFL) increase with damage to axons, extensions of neurons. (scitechdaily.com)
  • Glial fibrillary acidic protein (GFAP) is a measure of damage to glial cells, which support neurons. (scitechdaily.com)
  • Other investigators are focusing on how blood levels of a protein called neurofilament light chain (NfL) can predict brain atrophy and response to treatment in MS. NfL is a "scaffolding protein" that helps give form to neurons. (mymsaa.org)
  • Furthermore, evidence of reactive sprouting was observed within both grey and white matter axons, supporting the existence of innate regenerative potential within CNS neurons under the inhibitory influences of reactive glia and heavy myelination. (edu.au)
  • Neurofilaments are normal proteins found in healthy neurons, that are increased in blood and cerebrospinal fluid when damage has been done to neurons or their axons and are a marker of neurodegeneration. (biopharmaglobal.com)
  • specialized intermediate filaments called neurofilaments comprise the structural framework that establishes the size and shape of nerve cell extensions called axons, which are essential for transmission of nerve impulses to other neurons and to muscle cells. (medlineplus.gov)
  • Information is received by the dendrite through an array of receptors on dendrite surface that react to transmitters released from the axon terminals of other neurons. (comoficar.com)
  • Sensory neurons differentiated from human induced pluripotent stem cells form ganglia like clusters (Brn3a, purple) and extend axons (neurofilament, green) in culture. (ox.ac.uk)
  • Here, we report the generation of a new mouse model of GAN that is based on crossing transgenic mice overexpressing peripherin (Prph) with mice knockout for The Gan;TgPer mice developed early onset sensory-motor deficits along with IF accumulations made up of NF proteins and of Prph, causing swelling of spinal neurons at a young age. (ulaval.ca)
  • Peripherin is a ~57 kDa intermediate filament subunit found initially in sensory neurons of the peripheral nervous systems, which gives the protein its name. (phosphosolutions.com)
  • Electrophysiologic recording and indirect immunofluorescence were combined to study localization of the medium-sized neurofilament 145 (NF145) component of the cytoskeleton in morphologically identified neurons in the myenteric and submucosal plexuses of the guinea pig enteric nervous system. (wustl.edu)
  • NfL is a subunit of neurofilaments (Nfs), which are cylindrical proteins exclusively located in the neuronal cytoplasm ( figure 1 ). (bmj.com)
  • Tertiary structure alterations accompanying pyrrole formation at certain critical lysine-epsilon-amine functions in the neurofilament subunit proteins were hypothesized to underlie the neuropathy. (cdc.gov)
  • It appears that the metabolism of neurofilaments is disturbed in Alzheimer's disease, as indicated by the presence of neurofilament epitopes in the neurofibrillary tangles, as well as by the severe reduction of the expression of the gene for the light neurofilament subunit of the neurofilament triplet in brains of Alzheimer's patients. (bvsalud.org)
  • Our work shows that measuring neurofilament light soon after head injury helps predict who will develop long-term problems. (alzheimersresearchuk.org)
  • This protein is commonly used as a biomarker of neuronal damage. (wikipedia.org)
  • Measuring the protein biomarker in the blood will provide a simpler, more accurate way to predict clinical outcomes and may help to identify those at higher risk of developing dementia. (alzheimersresearchuk.org)
  • This protein is commonly used as a biomarker of neuronal damage and susceptibility to amyotrophic lateral sclerosis (ALS) has been associated with mutations in this gene. (utsouthwestern.edu)
  • Biogen is seeking approval of tofersen under the FDA's accelerated approval pathway, based on the use of neurofilament as a surrogate biomarker that is reasonably likely to predict clinical benefit. (biopharmaglobal.com)
  • For their research, the scientists used the neurofilament light chain (NfL) as the blood biomarker for their test. (biomedwire.com)
  • A growing body of evidence suggests that the plasma concentration of the neurofilament light chain (NfL) might be considered a plasma biomarker for the screening of neurodegeneration in Alzheimer's disease (AD). (biomedcentral.com)
  • They consist of three distinct polypeptides, the neurofilament triplet. (bvsalud.org)
  • This involved an ordered sequence of morphological, neurochemical and ultrastructural changes to neurites, including specific alterations to neurofilament triplet proteins, as well as intimate associations between reactive processes and glial populations. (edu.au)
  • Localization of multiple O-linked N-acetylglucosamine moieties on neurofilament polypeptides L and M." J. Biol. (wikipedia.org)
  • The other slowly transported group of proteins, designated slow components b (SCb), has a transport rate of 2-3 mm/d and consists of many polypeptides, one of which is actin (4). (rupress.org)
  • Our analyses of the transport kinetics of the individual polypeptides of SCa and SCb indicate that (a) the polypeptides of SCa are transported coherently in the optic axons, (b) the polypeptides of SCb are also transported coherently but completely separately from the SCa polypeptides, and (c) the polypeptides of SCa differ completely from those comprising SCb. (rupress.org)
  • Neurofilaments set the axon diameter and, in interaction with myelin in myelinated axons, co-determine g ratio. (medillsb.com)
  • Nogo-A, a myelin-associated protein, inhibits neurite outgrowth and abates regeneration in the adult vertebrate central nervous system (CNS) and may play a role in maintaining neural pathways once established. (biomedcentral.com)
  • Adlkofer K, Frei R, Neuberg DH, Zielasek J, Toyka KV, Suter U. Heterozygous peripheral myelin protein 22-deficient mice are affected by a progressive demyelinating tomaculous neuropathy. (2medicalcare.com)
  • Anzini P, Neuberg DH, Schachner M, Nelles E, Willecke K, Zielasek J, Toyka KV, Suter U, Martini R. Structural abnormalities and deficient maintenance of peripheral nerve myelin in mice lacking the gap junction protein connexin 32. (2medicalcare.com)
  • 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)
  • Dendrites contain numerous orderly arrays of microtubules and fewer neurofilaments (see below). (comoficar.com)
  • Axons consist of neurofilaments (in green) and microtubules (in red). (medillsb.com)
  • Any process that modulates the rate, frequency, or extent of microtubule-based movement, the movement of organelles, other microtubules and other particles along microtubules, mediated by motor proteins. (mcw.edu)
  • Amyloid Beta 40 and 42 are proteins are known to build up in patients Alzheimer's disease. (scitechdaily.com)
  • Neurofilaments (Nf) consist of three types of protein chains, differing in molecular mass: a light chain (NfL) of 68 kD, an intermediate chain of 150 kD, and a heavy chain of 190 to 210 kD, and are major components of axonal cytoskeleton [ 6 ]. (biomedcentral.com)
  • In CNS and peripheral nervous system diseases associated with axonal injury or degeneration, the concentration of neurofilament light chain (NfL) has been found to increase in cerebrospinal fluid (CSF) and blood. (bmj.com)
  • They found that blood levels of neurofilament light tracked extremely well to brain atrophy and importantly predicted further nerve cell degeneration up to one year after the injury. (alzheimersresearchuk.org)
  • GDNF reduces apoptosis and tissue degeneration, supports expression of neurofilament protein, calcitonin gene-related peptide (CGRP) and growth associated protein 43. (sciencedaily.com)
  • Peripherin is not related to peripherin/RDS, a protein of the photoreceptor outer membrane mutations of which are causative of certain forms of slow retinal degeneration. (phosphosolutions.com)
  • Axonal degeneration is a critical, early event following TBI of all severities but whether axon degeneration is a driver of TBI remains unclear. (umassmed.edu)
  • Despite this significant societal impact, surprisingly little is known about the molecular mechanisms that actively drive axon degeneration in any context and particularly following TBI. (umassmed.edu)
  • In comparison to the transport profiles from unligated control nerves, in ligated nerves there was redistribution of radiolabeled neurofilament and tubulin proteins back toward the cell body during the 14 d experimental period. (jneurosci.org)
  • The slowest group of proteins, designated slow component a (SCa), has a transport rate of 0.25 mm/d and consists of tubulin and neurofilament protein. (rupress.org)
  • Neurofilaments comprise the exoskeleton and functionally maintain neuronal caliber. (wikipedia.org)
  • Neurofilaments comprise the axoskeleton and functionally maintain neuronal caliber. (utsouthwestern.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)
  • The author postulated that the carboxy terminal tail of the neurofilament was the critical target in gamma-diketone neuropathy. (cdc.gov)
  • PHENOTYPE: Mice homozygous for a knock-out allele exhibit decreased axon diameter and transport. (utsouthwestern.edu)
  • Nf are highly phosphorylated proteins, and the degree of this phosphorylation determines the axon diameter [ 6 ]. (biomedcentral.com)
  • This loss results in focal accumulation of membranous organelles in parts of the length of damaged axons where the axonal diameter is greater than normal to form axonal swellings. (nih.gov)
  • Blood levels of neurofilament light were found to be closely related to measures from diffusion MRI, an advanced type of imaging which also provides measures related to damage to axons. (alzheimersresearchuk.org)
  • Histopathologic examination reveals an encapsulated dermal nodule comprised of proliferating Schwann cells and axons arranged in bundles. (e-jyms.org)
  • However, trends have indicated that tofersen reduces cerebrospinal fluid (CSF) concentrations of SOD1 and plasma concentrations of neurofilament light chains, especially when it is administered early in the disease course. (uspharmacist.com)
  • When axons, or nerve fibers, are damaged, NfL is released and can be found in the cerebrospinal fluid (CSF) and peripheral blood. (mymsaa.org)
  • The tissue suspensions were sonicated well and centrifuged in a TL-100 ultracentrifuge (Beckman Instruments, Fullerton, CA) at 100,000 g for 1 h at 25°C, and the protein concentrations in the supernatants were determined. (sigmaaldrich.com)
  • We also analyzed HIV RNA in blood and CSF, IgG Index, CSF WBC counts, and CSF concentrations of β2-micoglobulin, neopterin, and neurofilament light chain protein (NfL). (biomedcentral.com)
  • Neurofilaments are type IV intermediate filament heteropolymers composed of light (NEFL), medium (this protein), and heavy (NEFH) chains. (wikipedia.org)
  • Neurofilament medium polypeptide (NF-M) is a protein that in humans is encoded by the NEFM gene. (wikipedia.org)
  • The accumulation of these neurofilaments distends the axon leading to the both motor and sensory impairment with eventual neurodegeneration. (journalmc.org)
  • Pathologic features of AD are characterized by persistent deposition of the intercellular amyloid β-peptide (Aβ) plaques and intracellular tau protein and impairment of the neuron-to-neuron synaptic communication and nutrient transportation inside neuron 3 . (nature.com)
  • A New Mouse Model of Giant Axonal Neuropathy with Overt Phenotypes and Neurodegeneration Driven by Neurofilament Disorganization. (ulaval.ca)
  • Anti-Neurofilament NF-H Antibody, clone TA51 is an antibody against Neurofilament NF-H for use in ELISA, IP, WB, IH. (sigmaaldrich.com)
  • They may also play a role in intracellular transport to axons and dendrites. (wikipedia.org)
  • This gene encodes the medium neurofilament protein. (wikipedia.org)
  • The primary defect is a mutation in the GAN gene, which codes for the protein, gigaxonin. (journalmc.org)
  • The SACS gene provides instructions for producing a protein called sacsin. (medlineplus.gov)
  • Mutations in the SACS gene cause the production of an unstable sacsin protein that does not function normally. (medlineplus.gov)
  • The immune-related DEOSGs and hub genes were identified by weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) analysis, respectively. (nature.com)
  • We relate these results to our general hypothesis that slow axonal transport represents the movements of structural complexes of proteins. (rupress.org)
  • White matter and myelinated axons have high structural proteins such as NFL, a good indicator of CNS infection and injury [ 2 , 7 ]. (e-cep.org)
  • On the other hand, treatment of the axonal area with minor elicited a substantial axon outgrowth and branching (Fig 3E, F). Addition of minor to both somatic and axonal compartments, which recapitulates tests in non-compartmentalized cell ethnicities, induced axonal elongation and branching. (cancerhugs.com)
  • Moreover, pharmacological or genetic activation of inositol-requiring enzyme 1α, a central regulator of ER stress, downregulated T-cadherin at the mRNA and protein levels as well as attenuated EV production. (bvsalud.org)
  • These data indicate that Nogo-A is a multifunctional protein with additional roles during CNS development that are disparate from its later role of neurite outgrowth inhibition in the adult CNS. (biomedcentral.com)
  • F?Club graph of the common acceleration of axon outgrowth in the existence or not of small. (cancerhugs.com)
  • It is unclear how the abnormal sacsin protein affects the brain and skeletal muscles but it likely impairs normal organization of intermediate filaments in cells, particularly neurofilaments, and disrupts neuron function. (medlineplus.gov)
  • It is well established that intermediate filament (IF) proteins are substrates for gigaxonin-mediated degradation. (ulaval.ca)
  • Peripherin is also a good diagnostic marker for ballooned axons seen in Lou Gehrig's disease (Amyotrophic lateral sclerosis) and some neuronally derived tumors (2). (phosphosolutions.com)
  • Neurofilament light chain (NfL) is a neuronal cytoplasmic protein highly expressed in large calibre myelinated axons. (bmj.com)
  • The cofirst author of this study, Dr. Ahmed Abdelhak, explained that a neurofilament light chain was one of the many proteins found primarily in axons, noting that when these axons got lost or damaged, tiny fractions of the proteins entered the blood stream. (biomedwire.com)
  • Interaction of lysosomes and calpain on neurofilament steady-state levels. (uml.edu)
  • We posit that sidearm loss may be mediated either through proteolysis of sidearms via activation of microM calpain or sidearm dephosphorylation via posttraumatic, altered interaction between protein phosphatases and kinase(s), or a combination of these two, after calcium influx, which occurs, at least in part, as a result of changes in the structure and functional state of the axolemma. (nih.gov)
  • We have identified two slowly moving groups of axonally transported proteins in guinea pig retinal ganglion cell axons (4). (rupress.org)
  • Adiponectin, a protein specifically secreted by adipocytes, circulates abundantly in the human bloodstream, but its concentration decreases under pathological conditions such as visceral fat accumulation. (bvsalud.org)
  • The reason is the lack of a physical mechanism for the reverse information flow from the axon terminal, which is required so that the cargo concentration at the terminal could influence the cargo concentration distribution in the axon. (asme.org)
  • The obtained results explain why slow axonal transport must be bidirectional to allow for the maintenance of concentration gradients along the axon length. (asme.org)
  • Dr. Ari J. Green, cosenior author of a recent study's cosenior author, theorizes that progression of disability in patients with multiple sclerosis is likely brought on by the effect of the loss of axons and connections from important circuits that underlie crucial neurological functions. (biomedwire.com)
  • Evidence for proteolysis of neurofilaments has been obtained recently in the optic nerve stretch injury model and is correlated with disruption of the axolemma. (nih.gov)
  • E?Phase-contrast pictures of motoneurons obtained 1 and 6 h following small addition (arrowheads indicate elongated axons). (cancerhugs.com)
  • In this multicentre study, the researchers began by detecting proteins that are important to the structure of the nerve cell axons. (alzheimersresearchuk.org)
  • Results Outcomes show NFH manifestation generally in most PGP9.5 fibers except people that have TH you need to include the wide manifestation of NFH in axons lacking MBP. (scienza-under-18.org)
  • Conclusions The manifestation of NFH generally in most axons suggests a myelinated Angiotensin I (human, mouse, rat) source for most pulpal afferents, as the existence of NaCh clusters in unmyelinated materials suggests an natural convenience of the unmyelinated sections of myelinated materials to create NaCh accumulations. (scienza-under-18.org)
  • Monoclonal Anti-Neurofilament 200 (Phos. (sigmaaldrich.com)
  • Taken collectively, these outcomes suggest that lots of the unmyelinated axons inside the dental care Mouse monoclonal to SYP pulp result from mother or father axons that are myelinated at even more proximal locations. (scienza-under-18.org)
  • Deterioration of the BBB is most likely multifactorial, with contributing factors including secretion of pro-inflammatory cytokines and viral proteins from infected cells, as well as direct invasion of the cells of the neurovascular unit especially pericytes and perivascular macrophages by HIV [ 2 ]. (biomedcentral.com)
  • The present study results indicated that compared with the same number of 2D-cultured cells, microtissue could secrete more nerve regeneration related cytokines to promote SCs proliferation and axons growth. (biomedcentral.com)
  • A third hypothesis, involving charge neutralization of neurofilament proteins, implicated the loss of positive charge following the pyrrolylation reaction as the critical molecular lesion. (cdc.gov)
  • With this research we take the chance to characterize the materials with NaCh accumulations at non-nodal sites to check the hypothesis how the unmyelinated sections of myelinated axons display an inherent capability to cluster NaChs. (scienza-under-18.org)
  • Here, we report computational studies of bidirectional transport in an axon, specifically focusing on predictions when the retrograde motor becomes dysfunctional. (asme.org)
  • We use two different models to simulate bidirectional transport in an axon: an anterograde-retrograde model, which neglects passive transport by diffusion in the cytosol, and a full slow transport model, which includes passive transport by diffusion in the cytosol. (asme.org)
  • Perturbation analysis for the case when the retrograde motor velocity becomes close to zero predicts uniform cargo distributions along the axon. (asme.org)
  • Research on pathogenic mechanisms underlying giant axonal neuropathy (GAN), a disease caused by a deficiency of gigaxonin, has been hindered by the lack of appropriate animal models exhibiting substantial symptoms and large neurofilament (NF) swellings, a hallmark of the human disease. (ulaval.ca)
  • Research on pathogenic mechanism and treatment of GAN has been hampered by the lack of animal models exhibiting overt phenotypes and substantial neurofilament disorganization, a hallmark of the disease. (ulaval.ca)
  • We observed substantial brain pathology in SARS-CoV-2-infected dogs, particularly involving blood-brain barrier damage resembling small vessel disease, including changes in tight junction proteins, reduced laminin levels, and decreased pericyte coverage. (cdc.gov)
  • Neurofilaments Form Helical, Flexible Bundles During Neuritogenesis in Culture and Mature Axons in Situ. (uml.edu)
  • Small tumor-like overgrowths of axons, termed axonomas, were found in the central and peripheral nervous system, indicating attempted axonal regeneration. (nature.com)
  • They found that measuring blood levels of neurofilament light, a protein important for axonal structure provided a remarkably accurate long-term prognosis for the patient. (alzheimersresearchuk.org)
  • Protein aggregates of TDP43 have been found in the neuronal cytoplasm of 97% of ALS patients. (uspharmacist.com)
  • In ALS, higher levels of neurofilaments have been found to predict more rapid decline in clinical function and shortened survival. (biopharmaglobal.com)
  • The team also compared blood levels of neurofilament light with a special type of brain imaging that measures shrinkage (atrophy) of the brain, indicating the loss of nerve cells. (alzheimersresearchuk.org)
  • Elevated levels of this protein were also associated with an increased risk of worsening disability with no flare ups. (biomedwire.com)
  • Elevated or rising protein levels on serial lumbar punctures and 10 or fewer mononuclear cells/mm 3 strongly support the diagnosis. (medscape.com)
  • Tofersen study results suggest reductions in neurofilament preceded and predicted slowing of decline in measures of clinical and respiratory function, strength and quality of life. (biopharmaglobal.com)
  • to recognize all nerve materials, tyrosine hydroxylase (TH) to recognize sympathetic materials, contactin-associated proteins (caspr) to recognize nodal sites, S-100 to recognize Schwann cells and sodium stations (NaChs). (scienza-under-18.org)
  • The majority of these fibers were identified as sympathetic postganglionic axons based on their disappearance in organotypic culture and on their expression of tyrosine hydroxylase. (wustl.edu)
  • Many of these cell inclusions are responsible for the expression of genetic information controlling the synthesis of cellular proteins involved in energy production, growth, and replacement of materials lost by attrition. (comoficar.com)