Type III intermediate filament proteins that assemble into neurofilaments, the major cytoskeletal element in nerve axons and dendrites. They consist of three distinct polypeptides, the neurofilament triplet. Types I, II, and IV intermediate filament proteins form other cytoskeletal elements such as keratins and lamins. 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. (Can J Neurol Sci 1990 Aug;17(3):302)
Filaments 7-11 nm in diameter found in the cytoplasm of all cells. Many specific proteins belong to this group, e.g., desmin, vimentin, prekeratin, decamin, skeletin, neurofilin, neurofilament protein, and glial fibrillary acid protein.
Cytoplasmic filaments intermediate in diameter (about 10 nanometers) between the microfilaments and the microtubules. They may be composed of any of a number of different proteins and form a ring around the cell nucleus.
The directed transport of ORGANELLES and molecules along nerve cell AXONS. Transport can be anterograde (from the cell body) or retrograde (toward the cell body). (Alberts et al., Molecular Biology of the Cell, 3d ed, pG3)
Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body.
A prion disease found exclusively among the Fore linguistic group natives of the highlands of NEW GUINEA. The illness is primarily restricted to adult females and children of both sexes. It is marked by the subacute onset of tremor and ataxia followed by motor weakness and incontinence. Death occurs within 3-6 months of disease onset. The condition is associated with ritual cannibalism, and has become rare since this practice has been discontinued. Pathologic features include a noninflammatory loss of neurons that is most prominent in the cerebellum, glial proliferation, and amyloid plaques. (From Adams et al., Principles of Neurology, 6th ed, p773)
Subcellular structures found in nerve cell bodies and DENDRITES. They consist of granular endoplasmic reticulum (ENDOPLASMIC RETICULUM, ROUGH) and RIBOSOMES.
The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm.
The delicate interlacing threads, formed by aggregations of neurofilaments and neurotubules, coursing through the CYTOPLASM of the body of a NEURON and extending from one DENDRITE into another or into the AXON.
A superorder of CEPHALOPODS comprised of squid, cuttlefish, and their relatives. Their distinguishing feature is the modification of their fourth pair of arms into tentacles, resulting in 10 limbs.
A cylindrical column of tissue that lies within the vertebral canal. It is composed of WHITE MATTER and GRAY MATTER.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
An intermediate filament protein found in most differentiating cells, in cells grown in tissue culture, and in certain fully differentiated cells. Its insolubility suggests that it serves a structural function in the cytoplasm. MW 52,000.
The sum of the weight of all the atoms in a molecule.
'Nerve tissue proteins' are specialized proteins found within the nervous system's biological tissue, including neurofilaments, neuronal cytoskeletal proteins, and neural cell adhesion molecules, which facilitate structural support, intracellular communication, and synaptic connectivity essential for proper neurological function.
An intermediate filament protein found only in glial cells or cells of glial origin. MW 51,000.
Type III intermediate filament proteins expressed mainly in neurons of the peripheral and CENTRAL NERVOUS SYSTEMS. Peripherins are implicated in neurite elongation during development and axonal regeneration after injury.
A nerve which originates in the lumbar and sacral spinal cord (L4 to S3) and supplies motor and sensory innervation to the lower extremity. The sciatic nerve, which is the main continuation of the sacral plexus, is the largest nerve in the body. It has two major branches, the TIBIAL NERVE and the PERONEAL NERVE.
A serine-threonine kinase that plays important roles in CELL DIFFERENTIATION; CELL MIGRATION; and CELL DEATH of NERVE CELLS. It is closely related to other CYCLIN-DEPENDENT KINASES but does not seem to participate in CELL CYCLE regulation.
The 2nd cranial nerve which conveys visual information from the RETINA to the brain. The nerve carries the axons of the RETINAL GANGLION CELLS which sort at the OPTIC CHIASM and continue via the OPTIC TRACTS to the brain. The largest projection is to the lateral geniculate nuclei; other targets include the SUPERIOR COLLICULI and the SUPRACHIASMATIC NUCLEI. Though known as the second cranial nerve, it is considered part of the CENTRAL NERVOUS SYSTEM.
Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
Sensory ganglia located on the dorsal spinal roots within the vertebral column. The spinal ganglion cells are pseudounipolar. The single primary branch bifurcates sending a peripheral process to carry sensory information from the periphery and a central branch which relays that information to the spinal cord or brain.
Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.
A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from SPERM FLAGELLUM; CILIA; and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to COLCHICINE; VINCRISTINE; and VINBLASTINE.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including NEUROPEPTIDES; CYTOSKELETAL PROTEINS; proteins from SMOOTH MUSCLE; CARDIAC MUSCLE; liver; platelets; and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. This enzyme was formerly listed as EC 3.4.22.4.
Changes in the amounts of various chemicals (neurotransmitters, receptors, enzymes, and other metabolites) specific to the area of the central nervous system contained within the head. These are monitored over time, during sensory stimulation, or under different disease states.
The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible.
Techniques for removal by adsorption and subsequent elution of a specific antibody or antigen using an immunosorbent containing the homologous antigen or antibody.
Study of intracellular distribution of chemicals, reaction sites, enzymes, etc., by means of staining reactions, radioactive isotope uptake, selective metal distribution in electron microscopy, or other methods.
A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51)
The resection or removal of the nerve to an organ or part. (Dorland, 28th ed)
Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways.
Neurons of the innermost layer of the retina, the internal plexiform layer. They are of variable sizes and shapes, and their axons project via the OPTIC NERVE to the brain. A small subset of these cells act as photoreceptors with projections to the SUPRACHIASMATIC NUCLEUS, the center for regulating CIRCADIAN RHYTHM.
Neurons which activate MUSCLE CELLS.
Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.
Sites on an antigen that interact with specific antibodies.
Factors which enhance the growth potentialities of sensory and sympathetic nerve cells.
Antibodies produced by a single clone of cells.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)
The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.
Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein TUBULIN and are influenced by TUBULIN MODULATORS.
A class of fibrous proteins or scleroproteins that represents the principal constituent of EPIDERMIS; HAIR; NAILS; horny tissues, and the organic matrix of tooth ENAMEL. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms a coiled-coil alpha helical structure consisting of TYPE I KERATIN and a TYPE II KERATIN, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. alpha-Keratins have been classified into at least 20 subtypes. In addition multiple isoforms of subtypes have been found which may be due to GENE DUPLICATION.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
The non-neuronal cells of the nervous system. They not only provide physical support, but also respond to injury, regulate the ionic and chemical composition of the extracellular milieu, participate in the BLOOD-BRAIN BARRIER and BLOOD-RETINAL BARRIER, form the myelin insulation of nervous pathways, guide neuronal migration during development, and exchange metabolites with neurons. Neuroglia have high-affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitters, but their role in signaling (as in many other functions) is unclear.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Elements of limited time intervals, contributing to particular results or situations.
Immunologic techniques based on the use of: (1) enzyme-antibody conjugates; (2) enzyme-antigen conjugates; (3) antienzyme antibody followed by its homologous enzyme; or (4) enzyme-antienzyme complexes. These are used histologically for visualizing or labeling tissue specimens.

Nerve terminal damage by beta-bungarotoxin: its clinical significance. (1/1047)

We report here original data on the biological basis of prolonged neuromuscular paralysis caused by the toxic phospholipase A2 beta-bungarotoxin. Electron microscopy and immunocytochemical labeling with anti-synaptophysin and anti-neurofilament have been used to show that the early onset of paralysis is associated with the depletion of synaptic vesicles from the motor nerve terminals of skeletal muscle and that this is followed by the destruction of the motor nerve terminal and the degeneration of the cytoskeleton of the intramuscular axons. The postjunctional architecture of the junctions were unaffected and the binding of fluorescein-isothiocyanate-conjugated alpha-bungarotoxin to acetylcholine receptor was not apparently affected by exposure to beta-bungarotoxin. The re-innervation of the muscle fiber was associated by extensive pre- and post-terminal sprouting at 3 to 5 days but was stable by 7 days. Extensive collateral innervation of adjacent muscle fibers was a significant feature of the re-innervated neuromuscular junctions. These findings suggest that the prolonged and severe paralysis seen in victims of envenoming bites by kraits (elapid snakes of the genus Bungarus) and other related snakes of the family Elapidae is caused by the depletion of synaptic vesicles from motor nerve terminals and the degeneration of the motor nerve terminal and intramuscular axons.  (+info)

ELAV tumor antigen, Hel-N1, increases translation of neurofilament M mRNA and induces formation of neurites in human teratocarcinoma cells. (2/1047)

Human ELAV proteins are implicated in cell growth and differentiation via regulation of mRNA expression in the cytoplasm. In human embryonic teratocarcinoma (hNT2) cells transfected with the human neuronal ELAV-like protein, Hel-N1, neurites formed, yet cells were not terminally differentiated. Cells in which neurite formation was associated with Hel-N1 overexpression, also expressed increased levels of endogenous neurofilament M (NF-M) protein, which distributed along the neurites. However, steady-state levels of NF-M mRNA remained similar whether or not hNT2 cells were transfected with Hel-N1. These findings suggest that turnover of NF-M mRNA was not affected by Hel-N1 expression, despite the fact that Hel-N1 can bind to the 3' UTR of NF-M mRNA and was found directly associated with NF-M mRNA in transfected cells. Analysis of the association of NF-M mRNA with the translational apparatus in Hel-N1 transfectants showed nearly complete recruitment to heavy polysomes, indicating that Hel-N1 caused an increase in translational initiation. Our results suggest that the stability and/or translation of ARE-containing mRNAs can be regulated independently by the ELAV protein, Hel-N1, depending upon sequence elements in the 3' UTRs and upon the inherent turnover rates of the mRNAs that are bound to Hel-N1 in vivo.  (+info)

Deamidation and isoaspartate formation in smeared tau in paired helical filaments. Unusual properties of the microtubule-binding domain of tau. (3/1047)

An extensive loss of a selected population of neurons in Alzheimer's disease is closely related to the formation of paired helical filaments (PHFs). The most striking characteristic of PHFs upon Western blotting is their smearing. According to a previously described protocol (Morishima-Kawashima, M., Hasegawa, M., Takio, K., Suzuki, M., Titani, K., and Ihara, Y. (1993) Neuron 10, 1151-1160), smeared tau was purified, and its peptide map was compared with that of soluble (normal) tau. A CNBr fragment from soluble tau (CN5; residues 251-419 according to the 441-residue isoform) containing the microtubule-binding domain migrated at 15 and 18 kDa on SDS-polyacrylamide gel electrophoresis, whereas that from smeared tau exhibited two larger, unusually broad bands at approximately 30 and approximately 45 kDa, presumably representing dimers and trimers of CN5. In the peptide map of smeared tau-derived CN5, distinct peaks eluting at unusual locations were noted. Amino acid sequence and mass spectrometric analyses revealed that these distinct peptides bear isoaspartate at Asn-381 and Asp-387. Because no unusual peptides other than aspartyl or isoaspartyl peptide were found in the digests of smeared tau-derived CN5, it is likely that site-specific deamidation and isoaspartate formation are involved in its dimerization and trimerization and thus in PHF formation in vivo.  (+info)

Aberrant neurofilament phosphorylation in sensory neurons of rats with diabetic neuropathy. (4/1047)

Aberrant neurofilament phosphorylation occurs in many neurodegenerative diseases, and in this study, two animal models of type 1 diabetes--the spontaneously diabetic BB rat and the streptozocin-induced diabetic rat--have been used to determine whether such a phenomenon is involved in the etiology of the symmetrical sensory polyneuropathy commonly associated with diabetes. There was a two- to threefold (P < 0.05) elevation of neurofilament phosphorylation in lumbar dorsal root ganglia (DRG) of diabetic rats that was localized to perikarya of medium to large neurons using immunocytochemistry. Additionally, diabetes enhanced neurofilament M phosphorylation by 2.5-fold (P < 0.001) in sural nerve of BB rats. Neurofilaments are substrates of the mitogen-activated protein kinase (MAPK) family, which includes c-jun NH2-terminal kinase (JNK) or stress-activated protein kinase (SAPK1) and extracellular signal-regulated kinases (ERKs) 1 and 2. Diabetes induced a significant three- to fourfold (P < 0.05) increase in phosphorylation of a 54-kDa isoform of JNK in DRG and sural nerve, and this correlated with elevated c-Jun and neurofilament phosphorylation. In diabetes, ERK phosphorylation was also increased in the DRG, but not in sural nerve. Immunocytochemistry showed that JNK was present in sensory neuron perikarya and axons. Motoneuron perikarya and peroneal nerve of diabetic rats showed no evidence of increased neurofilament phosphorylation and failed to exhibit phosphorylation of JNK. It is hypothesized that in sensory neurons of diabetic rats, aberrant phosphorylation of neurofilament may contribute to the distal sensory axonopathy observed in diabetes.  (+info)

Overexpression of alpha-internexin causes abnormal neurofilamentous accumulations and motor coordination deficits in transgenic mice. (5/1047)

alpha-Internexin is the first neuronal intermediate filament (IF) protein expressed in postmitotic neurons of the developing nervous system. In the adult, its expression is restricted to mature neurons in the CNS. To study the potential role of alpha-internexin in neurodegeneration, we have generated transgenic mice that overexpress rat alpha-internexin. The total levels of alpha-internexin expressed in the hemizygous and homozygous transgenic mice were approximately 2 and approximately 3 times the normal level, respectively. Overexpression of alpha-internexin resulted in the formation of cerebellar torpedoes as early as 1 month of age. These torpedoes are abnormal swellings of Purkinje cell axons that are usually seen in neurodegenerative diseases involving the cerebellum. EM studies showed accumulations of high levels of IFs and abnormal organelles in the torpedoes and soma of Purkinje cells, as well as in the large pyramidal neurons of the neocortex and in the ventral anterior and posteromedial nuclei of the thalamus. Behavioral tests demonstrate that these mice have a deficit in motor coordination as early as 3 months of age, consistent with the morphological neuronal changes. Our data further demonstrate that the neurofilamentous inclusions also lead to progressive loss of neurons in the aged transgenic mice. The motor coordination deficit and the loss of neurons are transgene dosage-dependent. These data yield direct evidence that high levels of misaccumulated neuronal IFs lead to neuronal dysfunction, progressive neurodegeneration, and ultimate loss of neurons. Moreover, the degrees of neuronal dysfunction and degeneration are proportional to the levels of misaccumulated neuronal IFs.  (+info)

Development of the chick olfactory nerve. (6/1047)

Gonadotropin releasing hormone (GnRH) is produced and secreted by neurons dispersed throughout the septal-preoptic and anterior hypothalamic areas in adult birds and mammals. These neurons, essential for a functional brain-pituitary-gonadal axis, differentiate in the olfactory placode, the superior aspect of which forms the olfactory epithelium. To reach their final placement within the brain, GnRH neurons migrate out of the epithelium and along the olfactory nerve to the CNS. This nerve is essential for the entrance of GnRH neurons into the CNS. Due to the importance of the nerve for the proper migration of these neurons, we have used immunocytochemistry, DiI labeling and 1 microm serial plastic-embedded sections to characterize the nerve's earliest development in the embryonic chick (stages 17-21). Initially (stage 17) the zone between the placode and prosencephalon is a cellular mass contiguous with the placode. This cluster, known as epithelioid cells, is positive for some but not all neuronal markers studied. The epithelium itself is negative for all neuronal and glial markers at this early stage. By stage 18, the first neurites emerge from the epithelium; this was confirmed at stage 19 by examination of serial 1 microm plastic sections. There is sequential acquisition of immunoreactivity to neuronal markers from stage 18 to 21. The glial component of the nerve appears at stage 21. Axons originating from epithelium, extend to the border of the CNS as confirmed by DiI labeling at stage 21. Small fascicles have entered the CNS at this stage. As previously reported, GnRH neurons begin their migration between stages 20-21 and have also arrived at the border of the brain at stage 21. Despite the penetration of neurites from the olfactory nerve into the CNS, GnRH neurons pause at the nerve-brain junction until stage 29 (2 1/2 days later) before entering the brain. Subsequent studies will examine the nature of the impediment to continued GnRH neuronal migration.  (+info)

Claudin-11/OSP-based tight junctions of myelin sheaths in brain and Sertoli cells in testis. (7/1047)

Members of the newly identified claudin gene family constitute tight junction (TJ) strands, which play a pivotal role in compartmentalization in multicellular organisms. We identified oligodendrocyte-specific protein (OSP) as claudin-11, a new claudin family member, due to its sequence similarity to claudins as well as its ability to form TJ strands in transfected fibroblasts. Claudin-11/OSP mRNA was expressed in the brain and testis. Immunofluorescence microscopy with anti-claudin-11/OSP polyclonal antibody (pAb) and anti-neurofilament mAb revealed that in the brain claudin-11/OSP-positive linear structures run in a gentle spiral around neurofilament-positive axons. At the electron microscopic level, these linear structures were identified as the so-called interlamellar strands in myelin sheaths of oligodendrocytes. In testis, well-developed TJ strands of Sertoli cells were specifically labeled with anti-claudin-11/OSP pAb both at immunofluorescence and electron microscopic levels. These findings indicated that the interlamellar strands of oligodendrocyte myelin sheaths can be regarded as a variant of TJ strands found in many other epithelial cells, and that these strands share a specific claudin species, claudin-11/OSP, with those in Sertoli cells to create and maintain the repeated compartments around axons by oligodendrocytes.  (+info)

Activation of mitogen-activated protein kinases (Erk1 and Erk2) cascade results in phosphorylation of NF-M tail domains in transfected NIH 3T3 cells. (8/1047)

Neurofilaments (NFs) are neuron-specific intermediate filaments, and are the major cytoskeletal component in large myelinated axons. Lysine-serine-proline (KSP) repeats in the tail domains of high molecular weight NF proteins (NF-M and NF-H) are extensively phosphorylated in vivo in the axon. This phosphorylation in the tail domain has been postulated to play an important role in mediating neuron-specific properties, including axonal caliber and conduction velocity. Recent studies have shown that the mitogen-activated protein kinases (extracellular signal-regulated kinases, Erk1 and Erk2) phosphorylate KSP motifs in peptide substrates derived from the NF-M and NF-H tail domains in vitro. However, it is not clear whether activation of the mitogen activated protein (MAP) kinase pathway is able to phosphorylate these domains in vivo. To answer this question, a constitutively active form of mitogen-activated Erk activating kinase (MEK1) was cotransfected with an NF-M expression construct into NIH 3T3 cells. The activated mutant, but not the dominant negative mutant, induced phosphorylation of NF-M. In addition, it was shown that epidermal growth factor, which induces the MAP kinase cascade in NIH 3T3 cells, also activated endogenous Erk1 and Erk2 and NF-M tail domain phosphorylation in the transfected cells. These results present direct evidence that in-vivo activation of Erk1 and Erk 2 is sufficient for NF-M tail domain phosphorylation in transfected cells.  (+info)

Neurofilament proteins (NFs) are type IV intermediate filament proteins that are specific to neurons. They are the major structural components of the neuronal cytoskeleton and play crucial roles in maintaining the structural integrity, stability, and diameter of axons. Neurofilaments are composed of three subunits: light (NFL), medium (NFM), and heavy (NFH) neurofilament proteins, which differ in their molecular weights. These subunits assemble into heteropolymers to form the neurofilament core, while the C-terminal tails of NFH and NFM extend outward from the core, interacting with other cellular components and participating in various neuronal functions. Increased levels of neurofilament proteins, particularly NFL, in cerebrospinal fluid (CSF) and blood are considered biomarkers for axonal damage and neurodegeneration in several neurological disorders, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS).

Intermediate filament proteins (IFPs) are a type of cytoskeletal protein that form the intermediate filaments (IFs), which are one of the three major components of the cytoskeleton in eukaryotic cells, along with microtubules and microfilaments. These proteins have a unique structure, characterized by an alpha-helical rod domain flanked by non-helical head and tail domains.

Intermediate filament proteins are classified into six major types based on their amino acid sequence: Type I (acidic) and Type II (basic) keratins, Type III (desmin, vimentin, glial fibrillary acidic protein, and peripherin), Type IV (neurofilaments), Type V (lamins), and Type VI (nestin). Each type of IFP has a distinct pattern of expression in different tissues and cell types.

Intermediate filament proteins play important roles in maintaining the structural integrity and mechanical strength of cells, providing resilience to mechanical stress, and regulating various cellular processes such as cell division, migration, and signal transduction. Mutations in IFP genes have been associated with several human diseases, including cancer, neurodegenerative disorders, and genetic skin fragility disorders.

Intermediate filaments (IFs) are a type of cytoskeletal filament found in the cytoplasm of eukaryotic cells, including animal cells. They are called "intermediate" because they are smaller in diameter than microfilaments and larger than microtubules, two other types of cytoskeletal structures.

Intermediate filaments are composed of fibrous proteins that form long, unbranched, and flexible filaments. These filaments provide structural support to the cell and help maintain its shape. They also play a role in cell-to-cell adhesion, intracellular transport, and protection against mechanical stress.

Intermediate filaments are classified into six types based on their protein composition: Type I (acidic keratins), Type II (neutral/basic keratins), Type III (vimentin, desmin, peripherin), Type IV (neurofilaments), Type V (lamins), and Type VI (nestin). Each type of intermediate filament has a specific function and is expressed in different cell types. For example, Type I and II keratins are found in epithelial cells, while vimentin is expressed in mesenchymal cells.

Overall, intermediate filaments play an essential role in maintaining the structural integrity of cells and tissues, and their dysfunction has been implicated in various human diseases, including cancer, neurodegenerative disorders, and genetic disorders.

Axonal transport is the controlled movement of materials and organelles within axons, which are the nerve fibers of neurons (nerve cells). This intracellular transport system is essential for maintaining the structural and functional integrity of axons, particularly in neurons with long axonal processes. There are two types of axonal transport: anterograde transport, which moves materials from the cell body toward the synaptic terminals, and retrograde transport, which transports materials from the synaptic terminals back to the cell body. Anterograde transport is typically slower than retrograde transport and can be divided into fast and slow components based on velocity. Fast anterograde transport moves vesicles containing neurotransmitters and their receptors, as well as mitochondria and other organelles, at speeds of up to 400 mm/day. Slow anterograde transport moves cytoskeletal elements, proteins, and RNA at speeds of 1-10 mm/day. Retrograde transport is primarily responsible for recycling membrane components, removing damaged organelles, and transmitting signals from the axon terminal to the cell body. Dysfunctions in axonal transport have been implicated in various neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS).

An axon is a long, slender extension of a neuron (a type of nerve cell) that conducts electrical impulses (nerve impulses) away from the cell body to target cells, such as other neurons or muscle cells. Axons can vary in length from a few micrometers to over a meter long and are typically surrounded by a myelin sheath, which helps to insulate and protect the axon and allows for faster transmission of nerve impulses.

Axons play a critical role in the functioning of the nervous system, as they provide the means by which neurons communicate with one another and with other cells in the body. Damage to axons can result in serious neurological problems, such as those seen in spinal cord injuries or neurodegenerative diseases like multiple sclerosis.

Kuru is a rare, fatal neurological disorder that was identified in the Fore people of Papua New Guinea. It is primarily caused by an abnormal form of protein called prion and is transmitted through cannibalistic practices where infected human tissues are consumed. The disease is characterized by progressive deterioration of the brain, leading to symptoms such as tremors, difficulty coordinating movements, slurred speech, and uncontrollable laughter. There is currently no known cure for kuru, and it has become extremely rare due to the cessation of cannibalistic rituals in the affected population.

Nissl bodies, also known as Nissl substance or chromatophilic substance, are granular structures present in the cytoplasm of neurons. They are composed of rough endoplasmic reticulum and ribosomes, which are involved in protein synthesis. These bodies were first described by Franz Nissl in the late 19th century and are often used as a marker for neural degeneration in various neurological conditions. They stain deeply with basic dyes such as methylene blue or cresyl violet, making them visible under a microscope.

The cytoskeleton is a complex network of various protein filaments that provides structural support, shape, and stability to the cell. It plays a crucial role in maintaining cellular integrity, intracellular organization, and enabling cell movement. The cytoskeleton is composed of three major types of protein fibers: microfilaments (actin filaments), intermediate filaments, and microtubules. These filaments work together to provide mechanical support, participate in cell division, intracellular transport, and help maintain the cell's architecture. The dynamic nature of the cytoskeleton allows cells to adapt to changing environmental conditions and respond to various stimuli.

Neurofibrils are thin, thread-like structures found within the cytoplasm of nerve cells (neurons). They are primarily composed of various proteins and are involved in maintaining the structure and function of neurons. Neurofibrils include two types: neurofilaments and microtubule-associated protein tau (TAU) proteins.

Neurofilaments are intermediate filaments that provide structural support to neurons, while TAU proteins are involved in microtubule assembly, stability, and intracellular transport. Abnormal accumulation and aggregation of these proteins can lead to neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS).

Decapodiformes is a taxonomic order of marine cephalopods, which includes squids, octopuses, and cuttlefish. The name "Decapodiformes" comes from the Greek words "deca," meaning ten, and "podos," meaning foot, referring to the fact that these animals have ten limbs.

However, it is worth noting that within Decapodiformes, octopuses are an exception as they only have eight arms. The other members of this order, such as squids and cuttlefish, have ten appendages, which are used for locomotion, feeding, and sensory perception.

Decapodiformes species are known for their complex behaviors, sophisticated communication systems, and remarkable adaptations that enable them to thrive in a variety of marine habitats. They play important ecological roles as both predators and prey in the ocean food chain.

The spinal cord is a major part of the nervous system, extending from the brainstem and continuing down to the lower back. It is a slender, tubular bundle of nerve fibers (axons) and support cells (glial cells) that carries signals between the brain and the rest of the body. The spinal cord primarily serves as a conduit for motor information, which travels from the brain to the muscles, and sensory information, which travels from the body to the brain. It also contains neurons that can independently process and respond to information within the spinal cord without direct input from the brain.

The spinal cord is protected by the bony vertebral column (spine) and is divided into 31 segments: 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, and 1 coccygeal. Each segment corresponds to a specific region of the body and gives rise to pairs of spinal nerves that exit through the intervertebral foramina at each level.

The spinal cord is responsible for several vital functions, including:

1. Reflexes: Simple reflex actions, such as the withdrawal reflex when touching a hot surface, are mediated by the spinal cord without involving the brain.
2. Muscle control: The spinal cord carries motor signals from the brain to the muscles, enabling voluntary movement and muscle tone regulation.
3. Sensory perception: The spinal cord transmits sensory information, such as touch, temperature, pain, and vibration, from the body to the brain for processing and awareness.
4. Autonomic functions: The sympathetic and parasympathetic divisions of the autonomic nervous system originate in the thoracolumbar and sacral regions of the spinal cord, respectively, controlling involuntary physiological responses like heart rate, blood pressure, digestion, and respiration.

Damage to the spinal cord can result in various degrees of paralysis or loss of sensation below the level of injury, depending on the severity and location of the damage.

Neurons, also known as nerve cells or neurocytes, are specialized cells that constitute the basic unit of the nervous system. They are responsible for receiving, processing, and transmitting information and signals within the body. Neurons have three main parts: the dendrites, the cell body (soma), and the axon. The dendrites receive signals from other neurons or sensory receptors, while the axon transmits these signals to other neurons, muscles, or glands. The junction between two neurons is called a synapse, where neurotransmitters are released to transmit the signal across the gap (synaptic cleft) to the next neuron. Neurons vary in size, shape, and structure depending on their function and location within the nervous system.

Vimentin is a type III intermediate filament protein that is expressed in various cell types, including mesenchymal cells, endothelial cells, and hematopoietic cells. It plays a crucial role in maintaining cell structure and integrity by forming part of the cytoskeleton. Vimentin is also involved in various cellular processes such as cell division, motility, and intracellular transport.

In addition to its structural functions, vimentin has been identified as a marker for epithelial-mesenchymal transition (EMT), a process that occurs during embryonic development and cancer metastasis. During EMT, epithelial cells lose their polarity and cell-cell adhesion properties and acquire mesenchymal characteristics, including increased migratory capacity and invasiveness. Vimentin expression is upregulated during EMT, making it a potential target for therapeutic intervention in cancer.

In diagnostic pathology, vimentin immunostaining is used to identify mesenchymal cells and to distinguish them from epithelial cells. It can also be used to diagnose certain types of sarcomas and carcinomas that express vimentin.

Molecular weight, also known as molecular mass, is the mass of a molecule. It is expressed in units of atomic mass units (amu) or daltons (Da). Molecular weight is calculated by adding up the atomic weights of each atom in a molecule. It is a useful property in chemistry and biology, as it can be used to determine the concentration of a substance in a solution, or to calculate the amount of a substance that will react with another in a chemical reaction.

Nerve tissue proteins are specialized proteins found in the nervous system that provide structural and functional support to nerve cells, also known as neurons. These proteins include:

1. Neurofilaments: These are type IV intermediate filaments that provide structural support to neurons and help maintain their shape and size. They are composed of three subunits - NFL (light), NFM (medium), and NFH (heavy).

2. Neuronal Cytoskeletal Proteins: These include tubulins, actins, and spectrins that provide structural support to the neuronal cytoskeleton and help maintain its integrity.

3. Neurotransmitter Receptors: These are specialized proteins located on the postsynaptic membrane of neurons that bind neurotransmitters released by presynaptic neurons, triggering a response in the target cell.

4. Ion Channels: These are transmembrane proteins that regulate the flow of ions across the neuronal membrane and play a crucial role in generating and transmitting electrical signals in neurons.

5. Signaling Proteins: These include enzymes, receptors, and adaptor proteins that mediate intracellular signaling pathways involved in neuronal development, differentiation, survival, and death.

6. Adhesion Proteins: These are cell surface proteins that mediate cell-cell and cell-matrix interactions, playing a crucial role in the formation and maintenance of neural circuits.

7. Extracellular Matrix Proteins: These include proteoglycans, laminins, and collagens that provide structural support to nerve tissue and regulate neuronal migration, differentiation, and survival.

Glial Fibrillary Acidic Protein (GFAP) is a type of intermediate filament protein that is primarily found in astrocytes, which are a type of star-shaped glial cells in the central nervous system (CNS). These proteins play an essential role in maintaining the structural integrity and stability of astrocytes. They also participate in various cellular processes such as responding to injury, providing support to neurons, and regulating the extracellular environment.

GFAP is often used as a marker for astrocytic activation or reactivity, which can occur in response to CNS injuries, neuroinflammation, or neurodegenerative diseases. Elevated GFAP levels in cerebrospinal fluid (CSF) or blood can indicate astrocyte damage or dysfunction and are associated with several neurological conditions, including traumatic brain injury, stroke, multiple sclerosis, Alzheimer's disease, and Alexander's disease.

Peripherins are a family of neuron-specific type III intermediate filament proteins that are expressed in the peripheral nervous system. They play crucial roles in maintaining the structural integrity and stability of nerve cells, particularly during development and regeneration. Peripherins have also been implicated in various neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and Charcot-Marie-Tooth disease (CMT). There are several isoforms of peripherins, with peripherin 2 being the most widely studied. Mutations in the gene encoding peripherin 2 have been linked to certain forms of CMT.

The sciatic nerve is the largest and longest nerve in the human body, running from the lower back through the buttocks and down the legs to the feet. It is formed by the union of the ventral rami (branches) of the L4 to S3 spinal nerves. The sciatic nerve provides motor and sensory innervation to various muscles and skin areas in the lower limbs, including the hamstrings, calf muscles, and the sole of the foot. Sciatic nerve disorders or injuries can result in symptoms such as pain, numbness, tingling, or weakness in the lower back, hips, legs, and feet, known as sciatica.

Cyclin-Dependent Kinase 5 (CDK5) is a type of protein kinase that plays crucial roles in the regulation of various cellular processes, particularly in neurons. Unlike other cyclin-dependent kinases, CDK5 is activated by associating with regulatory subunits called cyclins, specifically cyclin I and cyclin D1, but not during the cell cycle.

CDK5 activity is primarily involved in the development and functioning of the nervous system, where it regulates neuronal migration, differentiation, and synaptic plasticity. It has been implicated in several neurological disorders, including Alzheimer's disease, Parkinson's disease, and various neurodevelopmental conditions.

CDK5 activity is tightly regulated by phosphorylation and interacting partners. Dysregulation of CDK5 can lead to abnormal neuronal function and contribute to the pathogenesis of neurological disorders.

The optic nerve, also known as the second cranial nerve, is the nerve that transmits visual information from the retina to the brain. It is composed of approximately one million nerve fibers that carry signals related to vision, such as light intensity and color, from the eye's photoreceptor cells (rods and cones) to the visual cortex in the brain. The optic nerve is responsible for carrying this visual information so that it can be processed and interpreted by the brain, allowing us to see and perceive our surroundings. Damage to the optic nerve can result in vision loss or impairment.

Electron microscopy (EM) is a type of microscopy that uses a beam of electrons to create an image of the sample being examined, resulting in much higher magnification and resolution than light microscopy. There are several types of electron microscopy, including transmission electron microscopy (TEM), scanning electron microscopy (SEM), and reflection electron microscopy (REM).

In TEM, a beam of electrons is transmitted through a thin slice of the sample, and the electrons that pass through the sample are focused to form an image. This technique can provide detailed information about the internal structure of cells, viruses, and other biological specimens, as well as the composition and structure of materials at the atomic level.

In SEM, a beam of electrons is scanned across the surface of the sample, and the electrons that are scattered back from the surface are detected to create an image. This technique can provide information about the topography and composition of surfaces, as well as the structure of materials at the microscopic level.

REM is a variation of SEM in which the beam of electrons is reflected off the surface of the sample, rather than scattered back from it. This technique can provide information about the surface chemistry and composition of materials.

Electron microscopy has a wide range of applications in biology, medicine, and materials science, including the study of cellular structure and function, disease diagnosis, and the development of new materials and technologies.

Phosphorylation is the process of adding a phosphate group (a molecule consisting of one phosphorus atom and four oxygen atoms) to a protein or other organic molecule, which is usually done by enzymes called kinases. This post-translational modification can change the function, localization, or activity of the target molecule, playing a crucial role in various cellular processes such as signal transduction, metabolism, and regulation of gene expression. Phosphorylation is reversible, and the removal of the phosphate group is facilitated by enzymes called phosphatases.

Spinal ganglia, also known as dorsal root ganglia, are clusters of nerve cell bodies located in the peripheral nervous system. They are situated along the length of the spinal cord and are responsible for transmitting sensory information from the body to the brain. Each spinal ganglion contains numerous neurons, or nerve cells, with long processes called axons that extend into the periphery and innervate various tissues and organs. The cell bodies within the spinal ganglia receive sensory input from these axons and transmit this information to the central nervous system via the dorsal roots of the spinal nerves. This allows the brain to interpret and respond to a wide range of sensory stimuli, including touch, temperature, pain, and proprioception (the sense of the position and movement of one's body).

The Fluorescent Antibody Technique (FAT) is a type of immunofluorescence assay used in laboratory medicine and pathology for the detection and localization of specific antigens or antibodies in tissues, cells, or microorganisms. In this technique, a fluorescein-labeled antibody is used to selectively bind to the target antigen or antibody, forming an immune complex. When excited by light of a specific wavelength, the fluorescein label emits light at a longer wavelength, typically visualized as green fluorescence under a fluorescence microscope.

The FAT is widely used in diagnostic microbiology for the identification and characterization of various bacteria, viruses, fungi, and parasites. It has also been applied in the diagnosis of autoimmune diseases and certain cancers by detecting specific antibodies or antigens in patient samples. The main advantage of FAT is its high sensitivity and specificity, allowing for accurate detection and differentiation of various pathogens and disease markers. However, it requires specialized equipment and trained personnel to perform and interpret the results.

Tubulin is a type of protein that forms microtubules, which are hollow cylindrical structures involved in the cell's cytoskeleton. These structures play important roles in various cellular processes, including maintaining cell shape, cell division, and intracellular transport. There are two main types of tubulin proteins: alpha-tubulin and beta-tubulin. They polymerize to form heterodimers, which then assemble into microtubules. The assembly and disassembly of microtubules are dynamic processes that are regulated by various factors, including GTP hydrolysis, motor proteins, and microtubule-associated proteins (MAPs). Tubulin is an essential component of the eukaryotic cell and has been a target for anti-cancer drugs such as taxanes and vinca alkaloids.

Immunohistochemistry (IHC) is a technique used in pathology and laboratory medicine to identify specific proteins or antigens in tissue sections. It combines the principles of immunology and histology to detect the presence and location of these target molecules within cells and tissues. This technique utilizes antibodies that are specific to the protein or antigen of interest, which are then tagged with a detection system such as a chromogen or fluorophore. The stained tissue sections can be examined under a microscope, allowing for the visualization and analysis of the distribution and expression patterns of the target molecule in the context of the tissue architecture. Immunohistochemistry is widely used in diagnostic pathology to help identify various diseases, including cancer, infectious diseases, and immune-mediated disorders.

Calpains are a family of calcium-dependent cysteine proteases that play important roles in various cellular processes, including signal transduction, cell death, and remodeling of the cytoskeleton. They are present in most tissues and can be activated by an increase in intracellular calcium levels. There are at least 15 different calpain isoforms identified in humans, which are categorized into two groups based on their calcium requirements for activation: classical calpains (calpain-1 and calpain-2) and non-classical calpains (calpain-3 to calpain-15). Dysregulation of calpain activity has been implicated in several pathological conditions, such as neurodegenerative diseases, muscular dystrophies, and cancer.

Brain chemistry refers to the chemical processes that occur within the brain, particularly those involving neurotransmitters, neuromodulators, and neuropeptides. These chemicals are responsible for transmitting signals between neurons (nerve cells) in the brain, allowing for various cognitive, emotional, and physical functions.

Neurotransmitters are chemical messengers that transmit signals across the synapse (the tiny gap between two neurons). Examples of neurotransmitters include dopamine, serotonin, norepinephrine, GABA (gamma-aminobutyric acid), and glutamate. Each neurotransmitter has a specific role in brain function, such as regulating mood, motivation, attention, memory, and movement.

Neuromodulators are chemicals that modify the effects of neurotransmitters on neurons. They can enhance or inhibit the transmission of signals between neurons, thereby modulating brain activity. Examples of neuromodulators include acetylcholine, histamine, and substance P.

Neuropeptides are small protein-like molecules that act as neurotransmitters or neuromodulators. They play a role in various physiological functions, such as pain perception, stress response, and reward processing. Examples of neuropeptides include endorphins, enkephalins, and oxytocin.

Abnormalities in brain chemistry can lead to various neurological and psychiatric conditions, such as depression, anxiety disorders, schizophrenia, Parkinson's disease, and Alzheimer's disease. Understanding brain chemistry is crucial for developing effective treatments for these conditions.

The brain is the central organ of the nervous system, responsible for receiving and processing sensory information, regulating vital functions, and controlling behavior, movement, and cognition. It is divided into several distinct regions, each with specific functions:

1. Cerebrum: The largest part of the brain, responsible for higher cognitive functions such as thinking, learning, memory, language, and perception. It is divided into two hemispheres, each controlling the opposite side of the body.
2. Cerebellum: Located at the back of the brain, it is responsible for coordinating muscle movements, maintaining balance, and fine-tuning motor skills.
3. Brainstem: Connects the cerebrum and cerebellum to the spinal cord, controlling vital functions such as breathing, heart rate, and blood pressure. It also serves as a relay center for sensory information and motor commands between the brain and the rest of the body.
4. Diencephalon: A region that includes the thalamus (a major sensory relay station) and hypothalamus (regulates hormones, temperature, hunger, thirst, and sleep).
5. Limbic system: A group of structures involved in emotional processing, memory formation, and motivation, including the hippocampus, amygdala, and cingulate gyrus.

The brain is composed of billions of interconnected neurons that communicate through electrical and chemical signals. It is protected by the skull and surrounded by three layers of membranes called meninges, as well as cerebrospinal fluid that provides cushioning and nutrients.

Electrophoresis, polyacrylamide gel (EPG) is a laboratory technique used to separate and analyze complex mixtures of proteins or nucleic acids (DNA or RNA) based on their size and electrical charge. This technique utilizes a matrix made of cross-linked polyacrylamide, a type of gel, which provides a stable and uniform environment for the separation of molecules.

In this process:

1. The polyacrylamide gel is prepared by mixing acrylamide monomers with a cross-linking agent (bis-acrylamide) and a catalyst (ammonium persulfate) in the presence of a buffer solution.
2. The gel is then poured into a mold and allowed to polymerize, forming a solid matrix with uniform pore sizes that depend on the concentration of acrylamide used. Higher concentrations result in smaller pores, providing better resolution for separating smaller molecules.
3. Once the gel has set, it is placed in an electrophoresis apparatus containing a buffer solution. Samples containing the mixture of proteins or nucleic acids are loaded into wells on the top of the gel.
4. An electric field is applied across the gel, causing the negatively charged molecules to migrate towards the positive electrode (anode) while positively charged molecules move toward the negative electrode (cathode). The rate of migration depends on the size, charge, and shape of the molecules.
5. Smaller molecules move faster through the gel matrix and will migrate farther from the origin compared to larger molecules, resulting in separation based on size. Proteins and nucleic acids can be selectively stained after electrophoresis to visualize the separated bands.

EPG is widely used in various research fields, including molecular biology, genetics, proteomics, and forensic science, for applications such as protein characterization, DNA fragment analysis, cloning, mutation detection, and quality control of nucleic acid or protein samples.

Cytoskeletal proteins are a type of structural proteins that form the cytoskeleton, which is the internal framework of cells. The cytoskeleton provides shape, support, and structure to the cell, and plays important roles in cell division, intracellular transport, and maintenance of cell shape and integrity.

There are three main types of cytoskeletal proteins: actin filaments, intermediate filaments, and microtubules. Actin filaments are thin, rod-like structures that are involved in muscle contraction, cell motility, and cell division. Intermediate filaments are thicker than actin filaments and provide structural support to the cell. Microtubules are hollow tubes that are involved in intracellular transport, cell division, and maintenance of cell shape.

Cytoskeletal proteins are composed of different subunits that polymerize to form filamentous structures. These proteins can be dynamically assembled and disassembled, allowing cells to change their shape and move. Mutations in cytoskeletal proteins have been linked to various human diseases, including cancer, neurological disorders, and muscular dystrophies.

Immunosorbent techniques are a group of laboratory methods used in immunology and clinical chemistry to isolate or detect specific proteins, antibodies, or antigens from a complex mixture. These techniques utilize the specific binding properties of antibodies or antigens to capture and concentrate target molecules.

The most common immunosorbent technique is the Enzyme-Linked Immunosorbent Assay (ELISA), which involves coating a solid surface with a capture antibody, allowing the sample to bind, washing away unbound material, and then detecting bound antigens or antibodies using an enzyme-conjugated detection reagent. The enzyme catalyzes a colorimetric reaction that can be measured and quantified, providing a sensitive and specific assay for the target molecule.

Other immunosorbent techniques include Radioimmunoassay (RIA), Immunofluorescence Assay (IFA), and Lateral Flow Immunoassay (LFIA). These methods have wide-ranging applications in research, diagnostics, and drug development.

Histochemistry is the branch of pathology that deals with the microscopic localization of cellular or tissue components using specific chemical reactions. It involves the application of chemical techniques to identify and locate specific biomolecules within tissues, cells, and subcellular structures. This is achieved through the use of various staining methods that react with specific antigens or enzymes in the sample, allowing for their visualization under a microscope. Histochemistry is widely used in diagnostic pathology to identify different types of tissues, cells, and structures, as well as in research to study cellular and molecular processes in health and disease.

Neuroblastoma is defined as a type of cancer that develops from immature nerve cells found in the fetal or early postnatal period, called neuroblasts. It typically occurs in infants and young children, with around 90% of cases diagnosed before age five. The tumors often originate in the adrenal glands but can also arise in the neck, chest, abdomen, or spine. Neuroblastoma is characterized by its ability to spread (metastasize) to other parts of the body, including bones, bone marrow, lymph nodes, and skin. The severity and prognosis of neuroblastoma can vary widely, depending on factors such as the patient's age at diagnosis, stage of the disease, and specific genetic features of the tumor.

Denervation is a medical term that refers to the loss or removal of nerve supply to an organ or body part. This can occur as a result of surgical intervention, injury, or disease processes that damage the nerves leading to the affected area. The consequences of denervation depend on the specific organ or tissue involved, but generally, it can lead to changes in function, sensation, and muscle tone. For example, denervation of a skeletal muscle can cause weakness, atrophy, and altered reflexes. Similarly, denervation of an organ such as the heart can lead to abnormalities in heart rate and rhythm. In some cases, denervation may be intentional, such as during surgical procedures aimed at treating chronic pain or spasticity.

Nerve degeneration, also known as neurodegeneration, is the progressive loss of structure and function of neurons, which can lead to cognitive decline, motor impairment, and various other symptoms. This process occurs due to a variety of factors, including genetics, environmental influences, and aging. It is a key feature in several neurological disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis. The degeneration can affect any part of the nervous system, leading to different symptoms depending on the location and extent of the damage.

Retinal Ganglion Cells (RGCs) are a type of neuron located in the innermost layer of the retina, the light-sensitive tissue at the back of the eye. These cells receive visual information from photoreceptors (rods and cones) via intermediate cells called bipolar cells. RGCs then send this visual information through their long axons to form the optic nerve, which transmits the signals to the brain for processing and interpretation as vision.

There are several types of RGCs, each with distinct morphological and functional characteristics. Some RGCs are specialized in detecting specific features of the visual scene, such as motion, contrast, color, or brightness. The diversity of RGCs allows for a rich and complex representation of the visual world in the brain.

Damage to RGCs can lead to various visual impairments, including loss of vision, reduced visual acuity, and altered visual fields. Conditions associated with RGC damage or degeneration include glaucoma, optic neuritis, ischemic optic neuropathy, and some inherited retinal diseases.

Motor neurons are specialized nerve cells in the brain and spinal cord that play a crucial role in controlling voluntary muscle movements. They transmit electrical signals from the brain to the muscles, enabling us to perform actions such as walking, talking, and swallowing. There are two types of motor neurons: upper motor neurons, which originate in the brain's motor cortex and travel down to the brainstem and spinal cord; and lower motor neurons, which extend from the brainstem and spinal cord to the muscles. Damage or degeneration of these motor neurons can lead to various neurological disorders, such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA).

"Cattle" is a term used in the agricultural and veterinary fields to refer to domesticated animals of the genus *Bos*, primarily *Bos taurus* (European cattle) and *Bos indicus* (Zebu). These animals are often raised for meat, milk, leather, and labor. They are also known as bovines or cows (for females), bulls (intact males), and steers/bullocks (castrated males). However, in a strict medical definition, "cattle" does not apply to humans or other animals.

An epitope is a specific region on the surface of an antigen (a molecule that can trigger an immune response) that is recognized by an antibody, B-cell receptor, or T-cell receptor. It is also commonly referred to as an antigenic determinant. Epitopes are typically composed of linear amino acid sequences or conformational structures made up of discontinuous amino acids in the antigen. They play a crucial role in the immune system's ability to differentiate between self and non-self molecules, leading to the targeted destruction of foreign substances like viruses and bacteria. Understanding epitopes is essential for developing vaccines, diagnostic tests, and immunotherapies.

Nerve Growth Factors (NGFs) are a family of proteins that play an essential role in the growth, maintenance, and survival of certain neurons (nerve cells). They were first discovered by Rita Levi-Montalcini and Stanley Cohen in 1956. NGF is particularly crucial for the development and function of the peripheral nervous system, which connects the central nervous system to various organs and tissues throughout the body.

NGF supports the differentiation and survival of sympathetic and sensory neurons during embryonic development. In adults, NGF continues to regulate the maintenance and repair of these neurons, contributing to neuroplasticity – the brain's ability to adapt and change over time. Additionally, NGF has been implicated in pain transmission and modulation, as well as inflammatory responses.

Abnormal levels or dysfunctional NGF signaling have been associated with various medical conditions, including neurodegenerative diseases (e.g., Alzheimer's and Parkinson's), chronic pain disorders, and certain cancers (e.g., small cell lung cancer). Therefore, understanding the role of NGF in physiological and pathological processes may provide valuable insights into developing novel therapeutic strategies for these conditions.

Monoclonal antibodies are a type of antibody that are identical because they are produced by a single clone of cells. They are laboratory-produced molecules that act like human antibodies in the immune system. They can be designed to attach to specific proteins found on the surface of cancer cells, making them useful for targeting and treating cancer. Monoclonal antibodies can also be used as a therapy for other diseases, such as autoimmune disorders and inflammatory conditions.

Monoclonal antibodies are produced by fusing a single type of immune cell, called a B cell, with a tumor cell to create a hybrid cell, or hybridoma. This hybrid cell is then able to replicate indefinitely, producing a large number of identical copies of the original antibody. These antibodies can be further modified and engineered to enhance their ability to bind to specific targets, increase their stability, and improve their effectiveness as therapeutic agents.

Monoclonal antibodies have several mechanisms of action in cancer therapy. They can directly kill cancer cells by binding to them and triggering an immune response. They can also block the signals that promote cancer growth and survival. Additionally, monoclonal antibodies can be used to deliver drugs or radiation directly to cancer cells, increasing the effectiveness of these treatments while minimizing their side effects on healthy tissues.

Monoclonal antibodies have become an important tool in modern medicine, with several approved for use in cancer therapy and other diseases. They are continuing to be studied and developed as a promising approach to treating a wide range of medical conditions.

An amino acid sequence is the specific order of amino acids in a protein or peptide molecule, formed by the linking of the amino group (-NH2) of one amino acid to the carboxyl group (-COOH) of another amino acid through a peptide bond. The sequence is determined by the genetic code and is unique to each type of protein or peptide. It plays a crucial role in determining the three-dimensional structure and function of proteins.

Alzheimer's disease is a progressive disorder that causes brain cells to waste away (degenerate) and die. It's the most common cause of dementia — a continuous decline in thinking, behavioral and social skills that disrupts a person's ability to function independently.

The early signs of the disease include forgetting recent events or conversations. As the disease progresses, a person with Alzheimer's disease will develop severe memory impairment and lose the ability to carry out everyday tasks.

Currently, there's no cure for Alzheimer's disease. However, treatments can temporarily slow the worsening of dementia symptoms and improve quality of life.

Antibody specificity refers to the ability of an antibody to bind to a specific epitope or antigenic determinant on an antigen. Each antibody has a unique structure that allows it to recognize and bind to a specific region of an antigen, typically a small portion of the antigen's surface made up of amino acids or sugar residues. This highly specific binding is mediated by the variable regions of the antibody's heavy and light chains, which form a pocket that recognizes and binds to the epitope.

The specificity of an antibody is determined by its unique complementarity-determining regions (CDRs), which are loops of amino acids located in the variable domains of both the heavy and light chains. The CDRs form a binding site that recognizes and interacts with the epitope on the antigen. The precise fit between the antibody's binding site and the epitope is critical for specificity, as even small changes in the structure of either can prevent binding.

Antibody specificity is important in immune responses because it allows the immune system to distinguish between self and non-self antigens. This helps to prevent autoimmune reactions where the immune system attacks the body's own cells and tissues. Antibody specificity also plays a crucial role in diagnostic tests, such as ELISA assays, where antibodies are used to detect the presence of specific antigens in biological samples.

Microtubules are hollow, cylindrical structures composed of tubulin proteins in the cytoskeleton of eukaryotic cells. They play crucial roles in various cellular processes such as maintaining cell shape, intracellular transport, and cell division (mitosis and meiosis). Microtubules are dynamic, undergoing continuous assembly and disassembly, which allows them to rapidly reorganize in response to cellular needs. They also form part of important cellular structures like centrioles, basal bodies, and cilia/flagella.

Keratins are a type of fibrous structural proteins that constitute the main component of the integumentary system, which includes the hair, nails, and skin of vertebrates. They are also found in other tissues such as horns, hooves, feathers, and reptilian scales. Keratins are insoluble proteins that provide strength, rigidity, and protection to these structures.

Keratins are classified into two types: soft keratins (Type I) and hard keratins (Type II). Soft keratins are found in the skin and simple epithelial tissues, while hard keratins are present in structures like hair, nails, horns, and hooves.

Keratin proteins have a complex structure consisting of several domains, including an alpha-helical domain, beta-pleated sheet domain, and a non-repetitive domain. These domains provide keratin with its unique properties, such as resistance to heat, chemicals, and mechanical stress.

In summary, keratins are fibrous structural proteins that play a crucial role in providing strength, rigidity, and protection to various tissues in the body.

Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.

Neuroglia, also known as glial cells or simply glia, are non-neuronal cells that provide support and protection for neurons in the nervous system. They maintain homeostasis, form myelin sheaths around nerve fibers, and provide structural support. They also play a role in the immune response of the central nervous system. Some types of neuroglia include astrocytes, oligodendrocytes, microglia, and ependymal cells.

"Cells, cultured" is a medical term that refers to cells that have been removed from an organism and grown in controlled laboratory conditions outside of the body. This process is called cell culture and it allows scientists to study cells in a more controlled and accessible environment than they would have inside the body. Cultured cells can be derived from a variety of sources, including tissues, organs, or fluids from humans, animals, or cell lines that have been previously established in the laboratory.

Cell culture involves several steps, including isolation of the cells from the tissue, purification and characterization of the cells, and maintenance of the cells in appropriate growth conditions. The cells are typically grown in specialized media that contain nutrients, growth factors, and other components necessary for their survival and proliferation. Cultured cells can be used for a variety of purposes, including basic research, drug development and testing, and production of biological products such as vaccines and gene therapies.

It is important to note that cultured cells may behave differently than they do in the body, and results obtained from cell culture studies may not always translate directly to human physiology or disease. Therefore, it is essential to validate findings from cell culture experiments using additional models and ultimately in clinical trials involving human subjects.

In the field of medicine, "time factors" refer to the duration of symptoms or time elapsed since the onset of a medical condition, which can have significant implications for diagnosis and treatment. Understanding time factors is crucial in determining the progression of a disease, evaluating the effectiveness of treatments, and making critical decisions regarding patient care.

For example, in stroke management, "time is brain," meaning that rapid intervention within a specific time frame (usually within 4.5 hours) is essential to administering tissue plasminogen activator (tPA), a clot-busting drug that can minimize brain damage and improve patient outcomes. Similarly, in trauma care, the "golden hour" concept emphasizes the importance of providing definitive care within the first 60 minutes after injury to increase survival rates and reduce morbidity.

Time factors also play a role in monitoring the progression of chronic conditions like diabetes or heart disease, where regular follow-ups and assessments help determine appropriate treatment adjustments and prevent complications. In infectious diseases, time factors are crucial for initiating antibiotic therapy and identifying potential outbreaks to control their spread.

Overall, "time factors" encompass the significance of recognizing and acting promptly in various medical scenarios to optimize patient outcomes and provide effective care.

Immunoenzyme techniques are a group of laboratory methods used in immunology and clinical chemistry that combine the specificity of antibody-antigen reactions with the sensitivity and amplification capabilities of enzyme reactions. These techniques are primarily used for the detection, quantitation, or identification of various analytes (such as proteins, hormones, drugs, viruses, or bacteria) in biological samples.

In immunoenzyme techniques, an enzyme is linked to an antibody or antigen, creating a conjugate. This conjugate then interacts with the target analyte in the sample, forming an immune complex. The presence and amount of this immune complex can be visualized or measured by detecting the enzymatic activity associated with it.

There are several types of immunoenzyme techniques, including:

1. Enzyme-linked Immunosorbent Assay (ELISA): A widely used method for detecting and quantifying various analytes in a sample. In ELISA, an enzyme is attached to either the capture antibody or the detection antibody. After the immune complex formation, a substrate is added that reacts with the enzyme, producing a colored product that can be measured spectrophotometrically.
2. Immunoblotting (Western blot): A method used for detecting specific proteins in a complex mixture, such as a protein extract from cells or tissues. In this technique, proteins are separated by gel electrophoresis and transferred to a membrane, where they are probed with an enzyme-conjugated antibody directed against the target protein.
3. Immunohistochemistry (IHC): A method used for detecting specific antigens in tissue sections or cells. In IHC, an enzyme-conjugated primary or secondary antibody is applied to the sample, and the presence of the antigen is visualized using a chromogenic substrate that produces a colored product at the site of the antigen-antibody interaction.
4. Immunofluorescence (IF): A method used for detecting specific antigens in cells or tissues by employing fluorophore-conjugated antibodies. The presence of the antigen is visualized using a fluorescence microscope.
5. Enzyme-linked immunosorbent assay (ELISA): A method used for detecting and quantifying specific antigens or antibodies in liquid samples, such as serum or culture supernatants. In ELISA, an enzyme-conjugated detection antibody is added after the immune complex formation, and a substrate is added that reacts with the enzyme to produce a colored product that can be measured spectrophotometrically.

These techniques are widely used in research and diagnostic laboratories for various applications, including protein characterization, disease diagnosis, and monitoring treatment responses.

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Neurofilament medium polypeptide (NF-M) is a protein that in humans is encoded by the NEFM gene. Neurofilaments are type IV ... This gene encodes the medium neurofilament protein. This protein is commonly used as a biomarker of neuronal damage. GRCh38: ... "Cytoplasmic O-GlcNAc modification of the head domain and the KSP repeat motif of the neurofilament protein neurofilament-H". J ... 1987). "The human mid-size neurofilament subunit: a repeated protein sequence and the relationship of its gene to the ...
... negative for neurofilament proteins). There is also considerable clinical interest in the use of neurofilament proteins as ... neurofilament proteins are released into the blood or cerebrospinal fluid. Immunoassays of neurofilament proteins in ... mammalian neurofilaments were originally thought to be composed of just three proteins called neurofilament protein NF-L (low ... The proteins that form neurofilaments are members of the intermediate filament protein family, which is divided into six types ...
The protein was originally purified from rat optic nerve and spinal cord. The protein copurifies with other neurofilament ... As development continues into neurons the neurofilament triplet proteins (NF-L: neurofilament low molecular mass, NF-M: ... along with the neurofilament triplet proteins. They are expressed in a relatively fixed stoichiometric ratio to neurofilaments ... α-internexin is functionally interdependent with the neurofilament triplet proteins. If one genetically deletes NF-M and/or NF- ...
Frappier T, Regnouf F, Pradel LA (1988). "Binding of brain spectrin to the 70-kDa neurofilament subunit protein". Eur. J. ... Secondly, another insert of 20 amino acids in the 10th spectrin repeat, termed SH3i+, contains protein kinase A and protein ... Herrmann H, Wiche G (1987). "Plectin and IFAP-300K are homologous proteins binding to microtubule-associated proteins 1 and 2 ... Ankyrin repeats of the multidomain Shank protein family interact with the cytoskeletal protein alpha-fodrin". J. Biol. Chem. ...
"PKN associates and phosphorylates the head-rod domain of neurofilament protein". J. Biol. Chem. 271 (16): 9816-22. doi:10.1074/ ... Serine/threonine-protein kinase N1 is an enzyme that in humans is encoded by the PKN1 gene. The protein encoded by this gene ... "PKN associates and phosphorylates the head-rod domain of neurofilament protein". J. Biol. Chem. 271 (16): 9816-22. doi:10.1074/ ... "Analysis of RhoA-binding proteins reveals an interaction domain conserved in heterotrimeric G protein beta subunits and the ...
For example, there is an increase in phosphorylated neurofilament proteins and cytoskeletal components, tubulin and actin, in ... Goldstein, ME; Cooper, HS; Bruce, J; Carden, MJ; Lee, VM; Schlaepfer, WW (1987). "Phosphorylation of neurofilament proteins and ... The increase in protein can be explained by the increase in cytoskeleton size. Changes in the cell body cytoskeleton seem to be ... Also both seem to be mechanically related to a disruption of the delivery of neurofilament to the axon due to a decreased ...
"TDP43 is a human low molecular weight neurofilament (hNFL) mRNA-binding protein". Molecular and Cellular Neurosciences. 35 (2 ... TAR DNA-binding protein 43 (TDP-43, transactive response DNA binding protein 43 kDa) is a protein that in humans is encoded by ... The entire protein devoid of large solubilising tags has been purified. The full-length protein is a dimer. The dimer is formed ... March 2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human ...
In contrast, structural proteins such as tubulin and neurofilament subunits are transported at lower rates. Proteins that are ... Microtubule Neurofilament Tubulin Microtubule associated protein Neuronal migration "Medical Definition of NEUROTUBULE". www. ... Microtubule-associated proteins (MAPs) are proteins that interact with microtubules by binding to their tubulin subunits and ... soluble protein. The speed of transport depends on the types of cargo to be transported. Neurotrophins, a family of proteins ...
Wild's research since 2017 has focused on the potential of neurofilament light and mutant huntingtin protein as biomarkers for ... "Evaluation of mutant huntingtin and neurofilament proteins as potential markers in Huntington's disease". Science Translational ... In 2015, he published the first successful detection and quantification of mutant huntingtin protein (the known cause of ... for the finding that neurofilament light in blood can predict onset and progression of HD). 2018 Elected Fellow of the Royal ...
"Peptidyl-Prolyl Isomerase 1 Regulates Protein Phosphatase 2A-Mediated Topographic Phosphorylation of Neurofilament Proteins". ... The enzyme binds to a subset of proteins and thus plays a role as a post phosphorylation control in regulating protein function ... Pin is a small protein at 18 kDa and does not have a nuclear localization or export signal. However, 2009, Lufei et al. ... "Entrez Gene: PIN1 Protein (peptidylprolyl cis/trans isomerase) NIMA-interacting 1". da Costa, Kauê Santana; Galúcio, João ...
"Effect of Guilingji on expression of neurofilament protein in cerebral cortex and corpus striatum". Chinese Journal of Anatomy ...
This includes synaptophysin, neurofilament protein, and CRX, a specific pineal or retinal marker, positive staining. Initial ...
Schmidt, M. L.; Lee, V. M.; Trojanowski, J. Q. (1989). "Analysis of epitopes shared by Hirano bodies and neurofilament proteins ... It was observed that Hirano bodies are a specific site of a C-terminal fragment of β-amyloid precursor proteins. University of ... More specifically the actin and actin binding proteins seen in Hirano bodies are a significant feature of an Alzheimer's ... Hirano bodies are intracellular aggregates of actin and actin-associated proteins first observed in neurons (nerve cells) by ...
"Characterization of the human superior olivary complex by calcium binding proteins and neurofilament H (SMI-32)". The Journal ... "Characterization of the rhesus monkey superior olivary complex by calcium binding proteins and synaptophysin". Journal of ...
A preliminary study about neurofilament light chain and tau protein levels in psoriasis: Correlation with disease severity. ... "A preliminary study about neurofilament light chain and tau protein levels in psoriasis: Correlation with disease severity." ... Okan and his team reported their findings that psoriasis patients had unusually high levels of neurofilament and Tau protein, ...
Neurofilament, heavy polypeptide (NEFH) is a protein that in humans is encoded by the NEFH gene. It is the gene for a heavy ... protein subunit that is combined with medium and light subunits to make neurofilaments, which form the framework for nerve ...
... proteins co-aggregate with spheroid neurofilaments in amyotrophic lateral sclerosis". Journal of Neuropathology and ... Microtubule-associated protein 6 (MAP6) or stable tubule-only polypeptide (STOP or STOP protein) is a protein that in humans is ... A MAP6-related protein, TbSAXO, has been discovered in Trypanosoma brucei. The domains of the protein responsible for ... This gene encodes a microtubule-associated protein (MAP). The encoded protein is a calmodulin binding, and calmodulin-regulated ...
... and these cells form interconnected axon networks and express tetanus toxin receptors and neurofilament proteins. By 10-14 days ... of NTERA-2 clonal human embryonal carcinoma cells into neurons involves the induction of all three neurofilament proteins". J ... as well as microtubule-associated proteins expressed in human neuroepithelium. NTERA-2 cells also accumulate cytoplasmic ...
"Myotubularin-related 2 protein phosphatase and neurofilament light chain protein, both mutated in CMT neuropathies, interact in ... The protein also contains a GRAM domain. Mutations in this gene are a cause of Charcot-Marie-Tooth disease type 4B, an ... The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 6 (3): 197-205. doi: ... Myotubularin-related protein 2 also known as phosphatidylinositol-3,5-bisphosphate 3-phosphatase or phosphatidylinositol-3- ...
Other molecules that can be degraded by calpains are microtubule subunits, microtubule-associated proteins, and neurofilaments ... as well as tau protein and amyloid precursor protein (APP) deposition. Lesions typically are found in the white matter of ... One of the proteins activated by the presence of calcium in the cell is calpain, a Ca2+-dependent non-lysosomal protease. About ... "Topography of axonal injury as defined by amyloid precursor protein and the sector scoring method in mild and severe closed ...
Activated p38 is able to recruit OGT to specific protein targets, including neurofilament H; O-GlcNAc modification of ... regulating protein-protein interactions, altering protein structure or enzyme activity, changing protein subcellular ... O-GlcNAc is almost exclusively found on nuclear and cytoplasmic proteins rather than membrane proteins and secretory proteins, ... Expressed protein ligation has been used to prepare O-GlcNAc-modified proteins in a site-specific manner. Methods exist for ...
Neurofilament light chain is a protein that is important in the growth and branching of neurons-cells found in the brain. In ... Atrophy of any tissue means a decrement in the size of the cell, which can be due to progressive loss of cytoplasmic proteins. ... Other biomarkers like Ng - a protein important in long-term potentiation and memory - have been tracked for their associations ... One study took advantage of biomarkers, namely one called neurofilament light chain (NFL), in patients with Alzheimer's disease ...
2000). "Association of synapse-associated protein 90/ postsynaptic density-95-associated protein (SAPAP) with neurofilaments". ... Disks large-associated protein 2 is a protein that in humans is encoded by the DLGAP2 gene. The product of this gene is one of ... 1997). "Characterization of guanylate kinase-associated protein, a postsynaptic density protein at excitatory synapses that ... This protein may play a role in the molecular organization of synapses and in neuronal cell signaling. Alternatively spliced ...
... and neurofilament protein. Some medulloblastomas may also display other forms of differentiation as demonstrated by the ... presence of the astrocytic marker glial fibrillary acidic protein. Skeletal muscle and melanocytic differentiation are ...
... microtubule-associated proteins, and neurofilaments. It may also damage ion channels, other enzymes, cell adhesion molecules, ... to recognize its common properties with two well-known proteins at the time, the calcium-regulated signalling protein, ... A calpain (/ˈkælpeɪn/; EC 3.4.22.52, EC 3.4.22.53) is a protein belonging to the family of calcium-dependent, non-lysosomal ... Amongst protein substrates, tertiary structure elements rather than primary amino acid sequences are likely responsible for ...
A Lewy body is composed of the protein alpha-synuclein associated with other proteins, such as ubiquitin, neurofilament protein ... Tau proteins may also be present, and Lewy bodies may occasionally be surrounded by neurofibrillary tangles. Lewy bodies and ... When misfolded proteins aggregate, or clump together, many diseases are more likely to develop, including those that are ... He was the first doctor to notice some unusual proteins in the brain, comparing them to earlier findings by Gonzalo Rodríguez ...
Several neuronal markers such as neurofilament proteins, HNK-1 antigen and tetanus toxin binding sites are expressed at highest ... "Bone morphogenetic proteins induce cardiomyocyte differentiation through the mitogen-activated protein kinase kinase kinase ... After 10 days of exposure, astroglial cells can be detected using glial fibrillary acidic protein (GFAP), which is a specific ... The main affected signaling pathway, bone morphogenetic proteins (BMPs) pathway is the most strongly studied signaling in P19 ...
Studies of extracted proteins suggest that this anemone's neurons contain neurofilament-like proteins that are molecularly ...
Finally, a loss of vesicular monoamine transporters, neurofilament proteins, and other morphological changes appear to indicate ...

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