The natural history of the myelin-derived nerve growth inhibitor Nogo-A

2008 ◽  
Vol 4 (2) ◽  
pp. 83-89 ◽  
Author(s):  
Rüdiger Schweigreiter

Nogo-A is possibly the best characterized myelin-derived inhibitor of nerve growth in the adult central nervous system (CNS). It is a member of the ancient reticulon family of mainly endoplasmic reticulum resident proteins with representatives found throughout the eukaryotic domain. Orthologs of the nogo gene were identified in tetrapods and teleost fish but none have been detected in invertebrates. Evolution of the nogo gene has been non-homogeneous. The exon–intron arrangement is conserved from amphibians (Xenopus) to mammals, but partly deviates from that found in several teleost fish species, indicating that the recruitment of nogo exons proceeded along at least two independent lines during early vertebrate evolution. This might have far-reaching consequences. Tetrapod nogo orthologs encode two neurite growth inhibitory domains whereas in fish nogo only one of the inhibitory domains is present. These distinct paths in nogo evolution have potentially contributed to the regeneration permissive CNS in fish as opposed to the non-regenerating CNS in higher vertebrates.

2016 ◽  
Vol 3 (1) ◽  
Author(s):  
Christian Macks ◽  
Jeoung Soo Lee

AbstractNeuronal axons damaged by traumatic injury are unable to spontaneously regenerate in the mammalian adult central nervous system (CNS), causing permanent motor, sensory, and cognitive deficits. Regenerative failure in the adult CNS results from a complex pathology presenting multiple barriers, both the presence of growth inhibitors in the extrinsic microenvironment and intrinsic deficiencies in neuronal biochemistry, to axonal regeneration and functional recovery. There are many strategies for axonal regeneration after CNS injury including antagonism of growth-inhibitory molecules and their receptors, manipulation of cyclic nucleotide levels, and delivery of growth-promoting stimuli through cell transplantation and neurotrophic factor delivery. While all of these approaches have achieved varying degrees of improvement in plasticity, regeneration, and function, there is no clinically effective therapy for CNS injury. RNA interference technology offers strategies for improving regeneration by overcoming the aspects of the injured CNS environment that inhibit neurite growth. This occurs through the knockdown of growth-inhibitory molecules and their receptors. In this review, we discuss the current state of RNAi strategies for the treatment of CNS injury based on non-viral vector mediated delivery.


Physiology ◽  
1998 ◽  
Vol 13 (6) ◽  
pp. 294-298 ◽  
Author(s):  
Martin E. Schwab

Neurite growth and regeneration in the adult central nervous system (CNS) is extremely limited. An important factor contributing to these restrictions is specific growth inhibitory proteins associated with oligodendrocytes and CNS myelin. A major inhibitory factor is the antigen of a monoclonal antibody; the application of this neutralizing antibody to spinal cord- or brain-lesioned adult rats induces long-distance regeneration of lesioned axons, as well as a specific increase in sprouting and rewiring of the cortical output system to the brain stem and the spinal cord. These anatomic changes are paralleled by important functional recoveries of locomotion and precision movements.


Author(s):  
Aluisio Rosa Gameiro Filho ◽  
Guilherme Sturzeneker ◽  
Ever Ernesto Caso Rodriguez ◽  
André Maia ◽  
Melina Correia Morales ◽  
...  

Abstract Background To report a case of acute exudative polymorphous paraneoplastic vitelliform maculopathy in a patient with a history of choroidal melanoma, with metastases to the pancreas, liver, and central nervous system. Case presentation A 63-year-old patient, with a history of enucleation of the right eye due to choroidal melanoma, complained of progressive visual loss during a follow-up visit. Fundoscopic examination revealed multiple small areas of serous retinal detachment scattered throughout the posterior pole and ancillary tests confirmed the diagnosis of acute exudative polymorphous paraneoplastic vitelliform maculopathy (AEPPVM). Screening for systemic metastases showed pancreatic, hepatic, and central nervous system involvement. Conclusions We describe a rare case of acute exudative polymorphous paraneoplastic vitelliform maculopathy, which should be considered in patients with or without a history of melanoma, who have vitelliform retinal detachments. Nevertheless, no previous reviews of literature have shown a correlation between AEPPVM and pancreatic metastasis.


1988 ◽  
Vol 107 (6) ◽  
pp. 2281-2291 ◽  
Author(s):  
P A Paganetti ◽  
P Caroni ◽  
M E Schwab

Differentiated oligodendrocytes and central nervous system (CNS) myelin are nonpermissive substrates for neurite growth and for cell attachment and spreading. This property is due to the presence of membrane-bound inhibitory proteins of 35 and 250 kD and is specifically neutralized by monoclonal antibody IN-1 (Caroni, P., and M. E. Schwab. 1988. Neuron. 1:85-96). Using rat optic nerve explants, CNS frozen sections, cultured oligodendrocytes or CNS myelin, we show here that highly invasive CNS tumor line (C6 glioblastoma) was not inhibited by these myelin-associated inhibitory components. Lack of inhibition was due to a specific mechanism as the metalloenzyme blocker 1,10-phenanthroline and two synthetic dipeptides containing metalloprotease-blocking sequences (gly-phe, tyr-tyr) specifically impaired C6 cell spreading on CNS myelin. In the presence of these inhibitors, C6 cells were affected by the IN-1-sensitive inhibitors in the same manner as control cells, e.g., 3T3 fibroblasts or B16 melanomas. Specific blockers of the serine, cysteine, and aspartyl protease classes had no effect. C6 cell spreading on inhibitor-free substrates such as CNS gray matter, peripheral nervous system myelin, glass, or poly-D-lysine was not sensitive to 1,10-phenanthroline. The nonpermissive substrate properties of CNS myelin were strongly reduced by incubation with a plasma membrane fraction prepared from C6 cells. This reduction was sensitive to the same inhibitors of metalloproteases. In our in vitro model for CNS white matter invasion, cell infiltration of optic nerve explants, which occurred with C6 cells but not with 3T3 fibroblasts or B16 melanomas, was impaired by the presence of the metalloprotease blockers. These results suggest that C6 cell infiltrative behavior in CNS white matter in vitro occurs by means of a metalloproteolytic activity, which probably acts on the myelin-associated inhibitory substrates.


Cancer ◽  
1981 ◽  
Vol 47 (1) ◽  
pp. 184-196 ◽  
Author(s):  
David J. Stewart ◽  
Michael J. Keating ◽  
Kenneth B. McCredie ◽  
Terry L. Smith ◽  
Eshan Youness ◽  
...  

PEDIATRICS ◽  
1965 ◽  
Vol 35 (4) ◽  
pp. 589-595
Author(s):  
John Lorber

1. The family histories of 722 infants who were born with spina bifida cystica were studied. 2. The index cases were referred for surgical treatment and were not selected in any way from the genetic point of view. 3. Intensive inquiries were made to obtain a complete family pedigree, including a prospective follow-up of siblings born after the index case. 4. Of 1,256 siblings 85 or 6.8% had gross malformation of the central nervous system: spina bifida cystica in 54, anencephaly in 22, and uncomplicated hydrocephalus in 9. 5. Of 306 children born after the index case 25 (8%) or 1 in 12 were affected. 6. There was a progressive increase in multiple cases in the family with increasing family size. In sibships of five or more, multiple cases occurred in 24.1%. 7. In 118 families cases of gross malformation of the central nervous system were known to have occurred among members of the family other than siblings. Cases occurred in three generations. 8. It is possible that spina bifida cystica might be a recessively inherited condition.


1973 ◽  
Vol 71 (1-2) ◽  
pp. 1-8 ◽  
Author(s):  
Sylvio Celso Goncalves da Costa ◽  
Samuel B. Pessoa ◽  
Neize de Moura Pereira ◽  
Tania Colombo

The main object of the present paper is to furnish a brief account to the knowledgement of Protozoa parasitic in common Brazilian frog of the genus Leptodactylus for general students in Zoology and for investigators that use this frog as a laboratory animal. Hepatozoon leptodactyli (Haemogregarina leptodactyli) was found in two species of frogs - Leptodactylus ocellatus and L. pentadactylus - in which develop schizogony whereas sporogony occurs in the leech Haementeria lutzi as was obtainded in experimental conditions. Intracellular forms have been found in peripheral circulation, chiefly in erythrocytes, but we have found them in leukocytes too. Tissue stages were found in frog, liver, lungs, spleen, gut, brain and heart. The occurence of hemogregarine in the Central Nervous System was recorded by Costa & al,(13) and Ball (2). Some cytochemical methods were employed in attempt to differentiate gametocytes from trophozoites in the peripheral blood and to characterize the cystic membrane as well. The speorogonic cycle was developed in only one specie of leech. A brief description of the parasite is given.


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