Multiple sclerosis (MS) is an encumbering inflammatory condition of the central nervous system (CNS) caused by axonal demyelination. There is sufficient evidence suggesting role of eukaryotic translation initiation factor 2B (EIF2B) gene family encoding the five subunits of eIF2B complex-α, β, γ, δ and ε respectively, in causing vanishing white matter (VWM) disease of the brain. Incidentally researchers have proposed overlapping between MS and VWM in terms of clinical, biochemical and genetic aspects, which incited us to write this chapter to explore the association between EIF2B5 and MS. eIF2B plays an essential role in translation initiation and its regulation in eukaryotes. Among EIF2B gene family, EIF2B5 gene encodes the catalytic and a crucial epsilon subunit of the eIF2B protein as most of the alterations have been found in this gene. The recent findings on the association between EIF2B5 and MS susceptibility point towards unfathomable and contentious role of EIF2B5 in MS development. This chapter briefly reviews the insights gleaned from recent studies conducted in understanding the association between EIF2B5 and MS risk. The need of hour is to conduct large scale conclusive studies aimed at expounding the mechanisms behind this relationship.
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http://dx.doi.org/10.1007/978-3-319-47861-6_5 | DOI Listing |
Transl Psychiatry
October 2024
Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Major depressive disorder (MDD) is a significant cause of disability in adults worldwide. However, the underlying causes and mechanisms of MDD are not fully understood, and many patients are refractory to available therapeutic options. Impaired control of brain mRNA translation underlies several neurodevelopmental and neurodegenerative conditions, including autism spectrum disorders and Alzheimer's disease (AD).
View Article and Find Full Text PDFCureus
July 2024
Genetics, National Institute of Neurology and Neurosurgery Manuel Velasco Suárez, Mexico City, MEX.
Leukodystrophies comprise a spectrum of genetic disorders affecting white matter (WM) formation in the central nervous system (CNS), of which vanishing white matter disease (VWMD) is one. VWMD presents with progressive neurological deterioration and a variety of manifestations. Ovarioleukodystrophy, a subtype of VWMD, exhibits a distinctive clinical profile encompassing both CNS WM alterations and ovarian dysfunction.
View Article and Find Full Text PDFJ Affect Disord
October 2024
School of Humanities, Southeast University, Nanjing 211189, China; Institute of Child Development and Education, Southeast University, Nanjing 211189, China; Key Laboratory of Child Development and Learning Science (Southeast University), Ministry of Education, Nanjing 211189, China. Electronic address:
For bipolar disorder (BD), the inconsistency of treatment guidelines and the long phases of pharmacological adjustment remain major challenges. BD is known to be comorbid with many medical and psychiatric conditions and they may share inflammatory and stress-related aetiologies, which could give rise to this association. The integrated stress response (ISR) responds to various stress conditions that lead to alterations in cellular homeostasis.
View Article and Find Full Text PDFNeuroradiology
September 2024
Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto - FMRP- USP, R. Ten. Catão Roxo, 3900 - Vila Monte Alegre, Ribeirão Preto, SP, 14015-010, Brazil.
Purpose: To characterize Vanishing White Matter Disease (VWM) cases from a Brazilian University Tertiary hospital, focusing on brain magnetic resonance image (MRI) aspects, clinical and molecular data.
Methods: Medical records and brain MRI of 13 genetically confirmed VWM patients were reviewed. Epidemiological data such as age at symptom onset, gender and main symptoms were analyzed, along with genetic mutations and MRI characteristics, such as the distribution of white matter lesions and atrophy.
Mol Ther
June 2024
Center for Gene Therapy, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH 43215, USA; Department of Pediatrics, The Ohio State University, Columbus, OH 43210, USA; Center for Clinical and Translational Science, The Ohio State University, Columbus, OH 43210, USA. Electronic address:
Leukoencephalopathy with vanishing white matter (VWM) is a progressive incurable white matter disease that most commonly occurs in childhood and presents with ataxia, spasticity, neurological degeneration, seizures, and premature death. A distinctive feature is episodes of rapid neurological deterioration provoked by stressors such as infection, seizures, or trauma. VWM is caused by autosomal recessive mutations in one of five genes that encode the eukaryotic initiation factor 2B complex, which is necessary for protein translation and regulation of the integrated stress response.
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