MRC Centre for Regenerative Medicine and MS Society/University of Edinburgh Centre for Translational Research, Scottish Centre for Regenerative Medicine, The University of Edinburgh, Edinburgh, United Kingdom.
Published: March 2015
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Article Abstract
The development and regeneration of myelin by oligodendrocytes, the myelin-forming cells of the central nervous system (CNS), requires profound changes in cell shape that lead to myelin sheath initiation and formation. Here, we demonstrate a requirement for the basal polarity complex protein Scribble in CNS myelination and remyelination. Scribble is expressed throughout oligodendroglial development and is up-regulated in mature oligodendrocytes where it is localised to both developing and mature CNS myelin sheaths. Knockdown of Scribble expression in cultured oligodendroglia results in disrupted morphology and myelination initiation. When Scribble expression is conditionally eliminated in the myelinating glia of transgenic mice, myelin initiation in CNS is disrupted, both during development and following focal demyelination, and longitudinal extension of the myelin sheath is disrupted. At later stages of myelination, Scribble acts to negatively regulate myelin thickness whilst suppressing the extracellular signal-related kinase (ERK)/mitogen-activated protein kinase (MAP) kinase pathway, and localises to non-compact myelin flanking the node of Ranvier where it is required for paranodal axo-glial adhesion. These findings demonstrate an essential role for the evolutionarily-conserved regulators of intracellular polarity in myelination and remyelination.
Central Laboratory of The Lishui Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui People's Hospital, Lishui, Zhejiang, China.
Introduction: Spinal cord injury (SCI) is a severe neurological disease characterized by significant motor, sensory, and autonomic dysfunctions. SCI is a major global disability cause, often resulting in long-term neurological impairments due to the impeded regeneration and remyelination of axons. A SCI interferes with communication between the brain and the spinal cord networks that control neurological functions.
Background: Oxidative stress and microglial activation are critical pathomechanisms in ischemic white matter injury. Microglia, as resident immune cells in the brain, are the main cells undergoing oxidative stress response. However, the role and molecular mechanism of oxidative stress in microglia have not been clearly elucidated during white matter ischemia.
Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Cuprizone-induced demyelination, wherein mice are fed a diet containing the copper chelator cuprizone, is a well-established model that replicates key features of demyelination and remyelination. However, the dose-response relationship of cuprizone is complex; high concentrations can induce toxicity, whereas low doses may fail to produce reliable demyelination across subjects.
Objective: Despite treatments which reduce relapses in multiple sclerosis (MS), many patients continue to experience progressive disability accumulation. MS is associated with metabolic disruptions and cerebral metabolic stress predisposes to tissue injury and possibly impaired remyelination. Additionally, myelin homeostasis is metabolically expensive and reliant on glycolysis.
Multiple sclerosis (MS) is a chronic, inflammatory demyelinating disorder of the central nervous system (CNS) targeting myelinated axons. Pathogenesis of MS entails an intricate genetic, environmental, and immunological interaction. Dysregulation of immune response i.
