Nogo-B is a major family member of the reticulon protein family 4. It is widely expressed in the central nervous system and peripheral tissues, and is mainly located in endoplasmic reticulum and cell membrane. Previous studies have revealed that Nogo-B plays a key role in vascular injury, tissue repair and inflammation process. It also may be critical for apoptosis of tumor cells and central diseases. Further investigation of the molecular characteristics and biological function of Nogo-B might be of great help to understand its role in diverse diseases.
Animals ; Apoptosis ; Cell Membrane ; physiology ; Endoplasmic Reticulum ; physiology ; Humans ; Inflammation ; Myelin Proteins ; physiology ; Nogo Proteins

Schizophrenia is likely to be a multifactorial disorder, consequence of alterations in gene and protein expression since the neurodevelopment that together to environmental factors will trigger the establishment of the disease. In the post-genomic era, proteomics has emerged as a promising strategy for revealing disease and treatment biomarkers as well as a tool for the comprehension of the mechanisms of schizophrenia pathobiology. Here, there is a discussion of the potential pathways and structures that are compromised in schizophrenia according to proteomic findings while studying five distinct brain regions of post-mortem tissue from schizophrenia patients and controls. Proteins involved in energy metabolism, calcium homeostasis, myelinization, and cytoskeleton have been recurrently found to be differentially expressed in schizophrenia brains. These findings may encourage new studies on the understanding of schizophrenia biochemical pathways and even new potential drug targets.
Biomarkers ; Brain ; Calcium ; Comprehension ; Cytoskeleton ; Energy Metabolism ; Homeostasis ; Humans ; Myelin Sheath ; Oligodendroglia ; Proteins ; Proteomics ; Schizophrenia

Dental pulp is innervated mostly by unmyelinated axons and small myelinated axons. These axons are implicated pain transmission and contain various neurotransmitters and receptors. However, little information, so far, is available on the distribution pattern and characterization of axons involved in the dental pain. In this study, to enhance understanding of dental pain processing, we observed distribution of axons expressing peripherin, an unmyelinated and small myelinated axonal marker, the in rat maxillary molar pulp. Peripherin-immunopositive (+) axons are mostly distributed in the peripheral pulp, and a few peripherin+ axons ascend into the odontoblast layer. Peripherin+ axons expressing NF200 are more frequently observed in the odontoblast layer (86.3+/-3.0%) than in the pulpal core region (79.3+/-2.8%) and nerve plexus region (78.6+/-1.9%). In contrast, peripherin+ axons expressing CGRP are less frequently observed in the odontoblast layer (17.7+/-5.0%) than in the pulpal core (37.7+/-10.1%) and nerve plexus regions (40.0+/-5.7%). These findings indicate that small myelinated axons are implicated in the transmission of dental pain arising from the odontoblast layer while peptidergic unmyelinated axons are implicated in the transmission of dental pain arising from central core and nerve plexus regions of the dental pulp.
Animals ; Axons ; Dental Pulp ; Intermediate Filament Proteins ; Membrane Glycoproteins ; Molar ; Myelin Sheath ; Nerve Tissue Proteins ; Neurotransmitter Agents ; Odontoblasts ; Rats

To study the inhibitory effect of Nogo-A shRNA on cell line PC12, the Nogo-A shRNA (short hairpin RNA, or shRNA) was designed and synthesized. The annealed shRNA template was inserted into plasmid pGenesil-1 containing enhanced green fluorescent protein (EGFP) gene by gene cloning technique to generate eukaryotic expression vector. The recombinant plasmid was transfected into PC12 cells by lipofecamine2000 and the mRNA and protein expression level of Nogo-A gene was detected by RT-PCR and Western blotting 48 h after the transfection. Gene sequencing showed that that the Nogo-A shRNA eukaryotic expression vector was successfully constructed. No significant change was found in the Nogo-A mRNA and protein expression level in empty vector-transfected group as compared with controls (P>0.05), while the expression level in shRNA-transfected group decreased significantly (P<0.05). It is concluded that the pGenesil-1/Nogo-AshRNA recombinant plasmid can effectively suppress the expression of Nogo-A gene in PC12 cells.
Cloning, Molecular ; Gene Knockdown Techniques/*methods ; Genetic Vectors ; Green Fluorescent Proteins/genetics ; Myelin Proteins/*genetics ; Myelin Proteins/metabolism ; PC12 Cells ; Plasmids ; RNA Interference ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; RNA, Small Interfering ; Transfection

OBJECTIVE: To compare the expression pattern of the MAL protein in normal and laryngeal carcinoma to derive possible implications of MAL in carcinoma development of larynx. METHOD: Use the immunohistochemical technique to analyze the distribution of MAL in normal laryngeal epithelial cells, polyp of vocal cords, laryngeal atypical hyperplasia and laryngeal squamous cell carcinoma. RESULT: MAL-like immunohistochemical reactions are strongly expressed in normal laryngeal epithelial cells and its expression is no significantly different in epithelial cells of the polyp of vocal cords. Comparatively, MAL expression is significantly down regulated in laryngeal atypical hyperplasia and laryngeal squamous cell carcinomas (P < 0.05). CONCLUSION MAL is normally expressed in laryngeal epithelial cells and its expression changes at early stages of carcinoma development. MAL, therefore, is a potential marker for early diagnosis of laryngeal squamous cell carcinoma.
Carcinoma, Squamous Cell ; metabolism ; pathology ; Case-Control Studies ; Double-Blind Method ; Epithelial Cells ; metabolism ; Humans ; Laryngeal Mucosa ; cytology ; metabolism ; Laryngeal Neoplasms ; metabolism ; pathology ; Membrane Transport Proteins ; metabolism ; Myelin Proteins ; metabolism ; Myelin and Lymphocyte-Associated Proteolipid Proteins ; Proteolipids ; metabolism

Myelin is a specialized structure of the nervous system that both enhances electrical conductance and insulates neurons from external risk factors. In the central nervous system, polarized oligodendrocytes form myelin by wrapping processes in a spiral pattern around neuronal axons through myelin-related gene regulation. Since these events occur at a distance from the cell body, post-transcriptional control of gene expression has strategic advantage to fine-tune the overall regulation of protein contents in situ. Therefore, many research interests have been focused to identify RNA binding proteins and their regulatory mechanism in myelinating compartments. Fragile X mental retardation protein (FMRP) is one such RNA binding protein, regulating its target expression by translational control. Although the majority of works on FMRP have been performed in neurons, it is also found in the developing or mature glial cells including oligodendrocytes, where its function is not well understood. Here, we will review evidences suggesting abnormal translational regulation of myelin proteins with accompanying white matter problem and neurological deficits in fragile X syndrome, which can have wider mechanistic and pathological implication in many other neurological and psychiatric disorders.
Axons ; Cell Body ; Central Nervous System ; Fragile X Mental Retardation Protein* ; Fragile X Syndrome ; Gene Expression ; Myelin Proteins* ; Myelin Sheath* ; Nervous System ; Neuroglia ; Neurons ; Oligodendroglia ; Risk Factors ; RNA-Binding Proteins ; White Matter

Myelin-forming oligodendrocytes in the central nervous system (CNS) and Schwann cells in the peripheral nervous system (PNS) are essential for structural and functional homeostasis of nervous tissue. Albeit with certain similarities, the regulation of CNS and PNS myelination is executed differently. Recent advances highlight the coordinated regulation of oligodendrocyte myelination by amino-acid sensing and growth factor signaling pathways. In this review, we discuss novel insights into the understanding of differential regulation of oligodendrocyte and Schwann cell biology in CNS and PNS myelination, with particular focus on the roles of growth factor-stimulated RHEB-mTORC1 and GATOR2-mediated amino-acid sensing/signaling pathways. We also discuss recent progress on the metabolic regulation of oligodendrocytes and Schwann cells and the impact of their dysfunction on neuronal function and disease.
Amino Acids ; Myelin Sheath/metabolism* ; Schwann Cells/metabolism* ; Oligodendroglia/metabolism* ; Signal Transduction ; Intercellular Signaling Peptides and Proteins/metabolism*

OBJECTIVETo delineate the clinical, electrophysiological and genetics features of a family where 4 members were affected with hereditary neuropathy with liability to pressure palsies (HNPP).

METHODSClinical features of the 4 patients were summarized. Electrophysiological examination and genetic analysis were carried out.

RESULTSAll of the patients showed recurrent motor and sensory disturbances after minor traction or constriction. Electrophysiology study revealed that the prolonged latency and reduced conduction velocity of peripheral nerve were general and with multiple sites of affection. The nerve locations liable to entrapment showed conduction block. A deletion mutation of peripheral myelin protein 22 (PMP22) gene was identified by genetic analysis.

CONCLUSIONHNPP usually affects areas where nerves are liable to entrapment, and presents with motor and sensory disturbances of the innervated areas. Electrophysiological study reveals general nervous demyelination. Genetic analysis can clarify the diagnosis of HNPP.

Adult ; Arthrogryposis ; genetics ; physiopathology ; Hereditary Sensory and Motor Neuropathy ; genetics ; physiopathology ; Humans ; Male ; Myelin Proteins ; genetics ; Neural Conduction

OBJECTIVETo study the mutation of PMP22 gene of an early-onset family with Charcot-Marie-Tooth disease (CMT) and the genetic features of the disease.

METHODSTwo patients with CMT, fifteen unaffected members in the family and 20 healthy controls were enrolled. STR-PCR and gene scanning were used to detect PMP22 duplication mutation.

RESULTSThe mutations of PMP22 were found in the two patients and other five unaffected members in the family. The mutations were located in the STR locus D17S921 in 5 cases and in the STR locus D17S4A in 2 cases. The other members in the family and 20 healthy controls did not show the mutations of PMP22.

CONCLUSIONSThe gene causing CMT in the family is found in the 17p11.2-p12 region containing PMP22 gene duplication mutation, resulting in the subtype CMT1A.

Charcot-Marie-Tooth Disease ; genetics ; Child ; Child, Preschool ; Chromosomes, Human, Pair 17 ; Female ; Humans ; Male ; Mutation ; Myelin Proteins ; genetics

Nerve regeneration after injury requires proper axon alignment to bridge the lesion site and myelination to achieve functional recovery. Transplanted scaffolds with aligned channels, have been shown to induce axon growth to some extent. However, the penetration of axons into the microchannels remain a challenge, influencing the functional recovery of regenerated nerves. We previously demonstrated that the size of microchannels exerts significant impact on Schwann cells (SCs) migration. Here we demonstrate that migration of SCs promotes, significantly, the dorsal root ganglion (DRG) neurons to extend axons into three-dimensional channels and form aligned fascicular-like axon tracts. Moreover, the migrating SCs attach and wrap around the aligned axons of DRG neurons in the microchannels and initiate myelination. The SCs release growth factors that provide chemotactic signals to the regenerating axons, similar to the response achieved with nerve growth factor (NGF), but with the additional capability of promoting myelination, thereby demonstrating the beneficial effects of including SCs over NGF alone in enhancing axon penetration and myelination in three-dimensional microchannels.
Axons* ; Diagnosis-Related Groups ; Ganglia, Spinal ; Intercellular Signaling Peptides and Proteins ; Myelin Sheath ; Nerve Growth Factor ; Nerve Regeneration ; Neurons ; Schwann Cells*