Leukodystrophies: a proposed classification system based on pathological changes and pathogenetic mechanisms.
TLDR
A novel classification of leukodystrophies is proposed that takes into account the primary involvement of any white matter component, and Categories in this classification are the myelin disorders due to a primary defect in oligodendrocytes or myelin; astrocytopathies; leuko-axonopathies; microgliopathy; andLeuko-vasculopathies.Abstract:
Leukodystrophies are genetically determined disorders characterized by the selective involvement of the central nervous system white matter. Onset may be at any age, from prenatal life to senescence. Many leukodystrophies are degenerative in nature, but some only impair white matter function. The clinical course is mostly progressive, but may also be static or even improving with time. Progressive leukodystrophies are often fatal, and no curative treatment is known. The last decade has witnessed a tremendous increase in the number of defined leukodystrophies also owing to a diagnostic approach combining magnetic resonance imaging pattern recognition and next generation sequencing. Knowledge on white matter physiology and pathology has also dramatically built up. This led to the recognition that only few leukodystrophies are due to mutations in myelin- or oligodendrocyte-specific genes, and many are rather caused by defects in other white matter structural components, including astrocytes, microglia, axons and blood vessels. We here propose a novel classification of leukodystrophies that takes into account the primary involvement of any white matter component. Categories in this classification are the myelin disorders due to a primary defect in oligodendrocytes or myelin (hypomyelinating and demyelinating leukodystrophies, leukodystrophies with myelin vacuolization); astrocytopathies; leuko-axonopathies; microgliopathies; and leuko-vasculopathies. Following this classification, we illustrate the neuropathology and disease mechanisms of some leukodystrophies taken as example for each category. Some leukodystrophies fall into more than one category. Given the complex molecular and cellular interplay underlying white matter pathology, recognition of the cellular pathology behind a disease becomes crucial in addressing possible treatment strategies.read more
Citations
More filters
Journal ArticleDOI
Myelin in the Central Nervous System: Structure, Function, and Pathology.
TL;DR: The biology of myelin, the expanded relationship of myelinating oligodendrocytes with its underlying axons and the neighboring cells, and its disturbances in various diseases such as multiple sclerosis, acute disseminated encephalomyelitis, and neuromyELitis optica spectrum disorders are reviewed.
Journal ArticleDOI
Homozygous Mutations in CSF1R Cause a Pediatric-Onset Leukoencephalopathy and Can Result in Congenital Absence of Microglia.
Nynke Oosterhof,Irene J. Chang,Ehsan Ghayoor Karimiani,Laura E. Kuil,Dana M. Jensen,Ray A. M. Daza,Erica Young,Lee Astle,Herma C. van der Linde,Giridhar M. Shivaram,Jeroen Demmers,Caitlin S. Latimer,C. Dirk Keene,Emily Loter,Reza Maroofian,Tjakko J. van Ham,Robert F. Hevner,James T. Bennett +17 more
TL;DR: The results suggest that CSF1R is required for human brain development and establish the csf1rDM fish as a model for microgliopathies and exemplify an under-recognized form of phenotypic expansion.
Journal ArticleDOI
White matter degeneration in vascular and other ageing-related dementias
TL;DR: It is demonstrated that WM degeneration encompasses multiple substrates and therefore more than one pharmacological approach is necessary to preserve axonal function and prevent cognitive impairment.
Journal ArticleDOI
CSF1R-related leukoencephalopathy: A major player in primary microgliopathies
TL;DR: The current knowledge of CSF1R-related leukoencephalopathy is addressed and the putative pathophysiology is discussed, with a focus on microglia, as well as future research directions.
Journal ArticleDOI
Astrocyte and Oligodendrocyte Cross-Talk in the Central Nervous System.
TL;DR: Emerging evidence of astrocyte-oligodendrocytes communication in health and disease is reviewed to reveal important insights into the pathogenesis and treatment of CNS diseases.
References
More filters
Journal ArticleDOI
Mitochondrial Hsp60 Chaperonopathy Causes an Autosomal-Recessive Neurodegenerative Disorder Linked to Brain Hypomyelination and Leukodystrophy
Daniella Magen,Costa Georgopoulos,Peter Bross,Debbie Ang,Yardena Segev,Yardena Segev,Dorit Goldsher,Dorit Goldsher,Alexandra Nemirovski,Eli Shahar,Eli Shahar,Sarit Ravid,Sarit Ravid,Anthony Luder,Bayan Heno,Ruth Gershoni-Baruch,Ruth Gershoni-Baruch,Karl Skorecki,Karl Skorecki,Hanna Mandel,Hanna Mandel +20 more
TL;DR: The findings suggest that Hsp60 defects can cause neurodegenerative pathologies of varying severity, not previously suspected on the basis of the SPG13 phenotype, which is termed MitCHAP-60 disease.
Journal ArticleDOI
Type III neuregulin-1 promotes oligodendrocyte myelination
Carla Taveggia,Pratik Thaker,Ashley Petrylak,Gregg L. Caporaso,Arrel D. Toews,Douglas L. Falls,Steven Einheber,James L. Salzer,James L. Salzer +8 more
TL;DR: It is indicated that oligodendrocyte myelination, but not differentiation, is promoted by axonal NRG1, underscoring important differences in the control of myelinations in the CNS and peripheral nervous system (PNS).
Journal ArticleDOI
GFAP mutations, age at onset, and clinical subtypes in Alexander disease
Morgan Prust,Jichuan Wang,Hiroki Morizono,Albee Messing,Michael Brenner,Erynn Gordon,Thomas R. Hartka,A. Sokohl,Raphael Schiffmann,Heather Gordish-Dressman,Roger L. Albin,H. Amartino,K. Brockman,A. Dinopoulos,M.T. Dotti,D. Fain,R. Fernandez,J. Ferreira,J. Fleming,D. Gill,M. Griebel,H. Heilstedt,Paige Kaplan,D. Lewis,M. Nakagawa,R. C. Pedersen,A. Reddy,Y. Sawaishi,M. Schneider,Elliott H. Sherr,Y. Takiyama,K. Wakabayashi,J. R. Gorospe,Adeline Vanderver +33 more
TL;DR: The proposed revised AxD subtypes, type I and type II, are proposed, based on analysis of statistically defined patient groups, with clear correlations to defined patterns of phenotypic expression.
Journal ArticleDOI
Axonal pathology in myelin disorders.
TL;DR: The data summarized in this review indicate that axonal damage is an integral part of myelin disease, and that loss of axons contributes to the irreversible functional impairment observed in affected individuals.
Journal ArticleDOI
Regulation of translation initiation factors by signal transduction
TL;DR: The cap-binding factor eukaryotic initiation factor (eIF)4E, its binding protein 4E-BP1, and the guanine-nucleotide-exchange factor eIF2B play important roles in the regulation of the rate of protein synthesis.
Related Papers (5)
Case Definition and Classification of Leukodystrophies and Leukoencephalopathies
Adeline Vanderver,Morgan Prust,Davide Tonduti,Fanny Mochel,Heather M. Hussey,Guy Helman,James Y. Garbern,Florian Eichler,Pierre Labauge,Patrick Aubourg,Diana Rodriguez,Marc C. Patterson,Johan L.K. Van Hove,Johanna L. Schmidt,Nicole I. Wolf,Odile Boespflug-Tanguy,Raphael Schiffmann,Marjo S. van der Knaap +17 more