Developmental hypomyelination in Wolfram syndrome: new insights from neuroimaging and gene expression analyses
| Autor: | Olga Neyman, Ahmad M. Samara, Amjad Samara, Ki Yun Park, Bess A. Marshall, Joseph D. Dougherty, Rachel M. Rahn, Tamara Hershey |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
endocrine system diseases Wolfram syndrome Neurodevelopment lcsh:Medicine Neuroimaging Review WFS1 endoplasmic reticulum stress Biology Endoplasmic Reticulum White matter Unfolded protein response 03 medical and health sciences Myelin 0302 clinical medicine medicine Animals Humans Pharmacology (medical) Neurodegeneration Genetics (clinical) Endoplasmic reticulum lcsh:R nutritional and metabolic diseases Brain Membrane Proteins Wolfram Syndrome General Medicine medicine.disease Oligodendrocyte Human genetics 030104 developmental biology medicine.anatomical_structure Neuroscience Hypomyelination 030217 neurology & neurosurgery |
| Zdroj: | Orphanet Journal of Rare Diseases Orphanet Journal of Rare Diseases, Vol 14, Iss 1, Pp 1-14 (2019) |
| ISSN: | 1750-1172 |
| Popis: | Wolfram syndrome is a rare multisystem disorder caused by mutations in WFS1 or CISD2 genes leading to brain structural abnormalities and neurological symptoms. These abnormalities appear in early stages of the disease. The pathogenesis of Wolfram syndrome involves abnormalities in the endoplasmic reticulum (ER) and mitochondrial dynamics, which are common features in several other neurodegenerative disorders. Mutations in WFS1 are responsible for the majority of Wolfram syndrome cases. WFS1 encodes for an endoplasmic reticulum (ER) protein, wolframin. It is proposed that wolframin deficiency triggers the unfolded protein response (UPR) pathway resulting in an increased ER stress-mediated neuronal loss. Recent neuroimaging studies showed marked alteration in early brain development, primarily characterized by abnormal white matter myelination. Interestingly, ER stress and the UPR pathway are implicated in the pathogenesis of some inherited myelin disorders like Pelizaeus-Merzbacher disease, and Vanishing White Matter disease. In addition, exploratory gene-expression network-based analyses suggest that WFS1 expression occurs preferentially in oligodendrocytes during early brain development. Therefore, we propose that Wolfram syndrome could belong to a category of neurodevelopmental disorders characterized by ER stress-mediated myelination impairment. Further studies of myelination and oligodendrocyte function in Wolfram syndrome could provide new insights into the underlying mechanisms of the Wolfram syndrome-associated brain changes and identify potential connections between neurodevelopmental disorders and neurodegeneration. |
| Databáze: | OpenAIRE |
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