Genetic disorders with central nervous system white matter abnormalities: An update

2020 ◽  
Vol 99 (1) ◽  
pp. 119-132
Author(s):  
Anju Shukla ◽  
Parneet Kaur ◽  
Dhanya Lakshmi Narayanan ◽  
Michelle C. do Rosario ◽  
Rajagopal Kadavigere ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
White Matter ◽  
Genetic Disorders ◽  
White Matter Abnormalities

Clinical and Genetic Spectrum of 104 Indian families with Central Nervous System White Matter Abnormalities

2021 ◽  
Author(s):  
Parneet Kaur ◽  
Michelle C. Rosario ◽  
Malavika Hebbar ◽  
Suvasini Sharma ◽  
Neethukrishna Kausthubham ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
White Matter ◽  
White Matter Abnormalities

scholarly journals The multicellular interplay of microglia in health and disease: lessons from leukodystrophy

2021 ◽  
Vol 14 (8) ◽  
Author(s):  
Woutje M. Berdowski ◽  
Leslie E. Sanderson ◽  
Tjakko J. van Ham
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
White Matter ◽  
Genetic Disorders ◽  
Brain Dysfunction ◽  
Brain Diseases ◽  
Human Patient ◽  
The Central Nervous System ◽  
The Impact

ABSTRACT Microglia are highly dynamic cells crucial for developing and maintaining lifelong brain function and health through their many interactions with essentially all cellular components of the central nervous system. The frequent connection of microglia to leukodystrophies, genetic disorders of the white matter, has highlighted their involvement in the maintenance of white matter integrity. However, the mechanisms that underlie their putative roles in these processes remain largely uncharacterized. Microglia have also been gaining attention as possible therapeutic targets for many neurological conditions, increasing the demand to understand their broad spectrum of functions and the impact of their dysregulation. In this Review, we compare the pathological features of two groups of genetic leukodystrophies: those in which microglial dysfunction holds a central role, termed ‘microgliopathies’, and those in which lysosomal or peroxisomal defects are considered to be the primary driver. The latter are suspected to have notable microglia involvement, as some affected individuals benefit from microglia-replenishing therapy. Based on overlapping pathology, we discuss multiple ways through which aberrant microglia could lead to white matter defects and brain dysfunction. We propose that the study of leukodystrophies, and their extensively multicellular pathology, will benefit from complementing analyses of human patient material with the examination of cellular dynamics in vivo using animal models, such as zebrafish. Together, this will yield important insight into the cell biological mechanisms of microglial impact in the central nervous system, particularly in the development and maintenance of myelin, that will facilitate the development of new, and refinement of existing, therapeutic options for a range of brain diseases.

Linfoistiocitosi eritrofagocitica

2003 ◽  
Vol 16 (3) ◽  
pp. 365-372 ◽  
Author(s):  
F. Caranci ◽  
A. D'Amico ◽  
F. Briganti ◽  
R. Migliorati ◽  
C. De Fusco ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Bone Marrow ◽  
Nervous System ◽  
White Matter ◽  
White Matter Abnormalities ◽  
Diffuse White Matter ◽  
Multisystem Involvement ◽  
Identification And Characterization

Erithrophagocytic lymphohistiocytosis is a rare disease characterized by exaggerated histiocytic proliferation and activation12 and multisystem involvement including visceral organs, lymph nodes, bone marrow and central nervous system4. Magnetic Resonance (MR) examination was performed in 10 patients with previously diagnosed Erithrophagocytic lymphohistiocytosis. This study was aimed at assessing MR accuracy in the identification and characterization of central nervous system lesions. MR findings show a good correlation with areas of parenchymal and meningeal lymphohistiocytic infiltration5, demonstrating diffuse white matter abnormalities in the early stages and necrotic areas with parenchymal volume loss as terminal findings4. In addition, MR allows the follow-up after chemotherapy and bone marrow transplantation2,3. Although rare, EL should be differentiated from other pediatric patchy white matter abnormalities5.

scholarly journals Glioblastoma infiltration into central nervous system tissue in vitro: involvement of a metalloprotease.

1988 ◽  
Vol 107 (6) ◽  
pp. 2281-2291 ◽  
Author(s):  
P A Paganetti ◽  
P Caroni ◽  
M E Schwab
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
White Matter ◽  
Optic Nerve ◽  
Cell Attachment ◽  
Neurite Growth ◽  
Cell Spreading ◽  
C6 Cells ◽  
3T3 Fibroblasts

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.

Neurotrophins and theirtrk receptors in cultured cells of the glial lineage and in white matter of the central nervous system

1995 ◽  
Vol 6 (4) ◽  
pp. 237-248 ◽  
Author(s):  
Daniele F. Condorelli ◽  
Tuija Salin ◽  
Paola Dell’Albani ◽  
Giuseppa Mudò ◽  
Massimo Corsaro ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
White Matter ◽  
Cultured Cells ◽  
The Central Nervous System ◽  
Glial Lineage

scholarly journals Membrane-type 1 Matrix Metalloprotease (MT1-MMP) Enables Invasive Migration of Glioma Cells in Central Nervous System White Matter

1999 ◽  
Vol 144 (2) ◽  
pp. 373-384 ◽  
Author(s):  
Ann T.J. Beliën ◽  
Paolo A. Paganetti ◽  
Martin E. Schwab
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
White Matter ◽  
Plasma Membranes ◽  
Malignant Gliomas ◽  
Glioma Cells ◽  
C6 Glioma ◽  
C6 Glioma Cells ◽  
Glioblastoma Cells

Invasive glioma cells migrate preferentially along central nervous system (CNS) white matter fiber tracts irrespective of the fact that CNS myelin contains proteins that inhibit cell migration and neurite outgrowth. Previous work has demonstrated that to migrate on a myelin substrate and to overcome its inhibitory effect, rat C6 and human glioblastoma cells require a membrane-bound metalloproteolytic activity (C6-MP) which shares several biochemical and pharmacological characteristics with MT1-MMP. We show now that MT1-MMP is expressed on the surface of rat C6 glioblastoma cells and is coenriched with C6-MP activity. Immunodepletion of C6-MP activity is achieved with an anti–MT1-MMP antibody. These data suggest that MT1-MMP and the C6-MP are closely related or identical. When mouse 3T3 fibroblasts were transfected with MT1-MMP they acquired the ability to spread and migrate on the nonpermissive myelin substrate and to infiltrate into adult rat optic nerve explants. MT1-MMP–transfected fibroblasts and C6 glioma cells were able to digest bNI-220, one of the most potent CNS myelin inhibitory proteins. Plasma membranes of both MT1-MMP–transfected fibroblasts and C6 glioma cells inactivated inhibitory myelin extracts, and this activity was sensitive to the same protease inhibitors. Interestingly, pretreatment of CNS myelin with gelatinase A/MMP-2 could not inactivate its inhibitory property. These data imply an important role of MT1-MMP in spreading and migration of glioma cells on white matter constituents in vitro and point to a function of MT1-MMP in the invasive behavior of malignant gliomas in the CNS in vivo.

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