1,721,228 research outputs found
White matter aging and its impact on brain function
Full text linkAging has a detrimental impact on white matter, resulting in reduced volume, compromised structural integrity of myelinated axons, and an increase in white matter hyperintensities. These changes are closely linked to cognitive decline and neurological disabilities. The deterioration of myelin and its diminished ability to regenerate as we age further contribute to the progression of neurodegenerative disorders. Understanding these changes is crucial for devising effective disease prevention strategies. Here, we will discuss the structural alterations in white matter that occur with aging and examine the cellular and molecular mechanisms driving these aging-related transformations. We highlight how the progressive disruption of white matter may initiate a self-perpetuating cycle of inflammation and neural damage
Exosomes - vesicular carriers for intercellular communication
No full textCells release different types of vesicular carriers of membrane and cytosolic components into the extracellular space. These vesicles are generated within the endosomal system or at the plasma membrane. Among the various kinds of secreted membrane vesicles, exosomes are vesicles with a diameter of 40-100 nm that are secreted upon fusion of multivesicular endosomes with the cell surface. Exosomes transfer not only membrane components but also nucleic acid between different cells, emphasizing their role in intercellular communication. This ability is likely to underlie the different physiological and pathological events, in which exosomes from different cell origins have been implicated. Only recently light have been shed on the subcellular compartments and mechanisms involved in their biogenesis and secretion opening new avenues to understand their functions.ER
Oligodendrocytes in Alzheimer's disease pathophysiology
No full textOur understanding of Alzheimer's disease (AD) has transformed from a purely neuronal perspective to one that acknowledges the involvement of glial cells. Despite remarkable progress in unraveling the biology of microglia, astrocytes and vascular elements, the exploration of oligodendrocytes in AD is still in its early stages. Contrary to the traditional notion of oligodendrocytes as passive bystanders in AD pathology, emerging evidence indicates their active participation in and reaction to amyloid and tau pathology. Oligodendrocytes undergo a functional transition to a disease-associated state, engaging in immune modulation, stress responses and cellular survival. Far from being inert players, they appear to serve a dual role in AD pathogenesis, potentially offering defense mechanisms against pathology while also contributing to disease progression. This Review explores recent advancements in understanding the roles of oligodendrocytes and their myelin sheaths in the context of AD, shedding light on their complex interactions within the disease pathology
Lipid metabolism and neuroinflammation: What is the link?
No full textLipid metabolism is central to host defense by supporting and modulating immune cell function. Immune signaling pathways control anabolic lipid processes to drive membrane synthesis and produce bioactive lipid mediators during activation. In turn, metabolic states profoundly influence immune signaling, particularly during the resolution of inflammation. Emerging evidence highlights a dynamic interplay between lipid metabolism and neuroinflammation. A striking example is the intrinsic lipoprotein system of the central nervous system, which undergoes profound changes during pathology, with lipoproteins serving not only in lipid transport but also as immune modulators and as contributors to disease tolerance. Importantly, major neurodegenerative diseases are genetically linked to disruptions in lipid metabolism. Deciphering this complex cross talk may provide opportunities for novel therapies targeting neuroinflammatory and neurodegenerative disorders
Chronic Progressive Multiple Sclerosis - Pathogenesis of Neurodegeneration and Therapeutic Strategies
No full textMultiple sclerosis (MS) is an inflammatory, autoimmune, demyelinating disease of the central nervous system (CNS) that usually starts as a relapsing-remitting disease. In most patients the disease evolves into a chronic progressive phase characterized by continuous accumulation of neurological deficits. While treatment of relapsing-remitting MS (RRMS) has improved dramatically over the last decade, the therapeutic options for chronic progressive MS, both primary and secondary, are still limited. In order to find new pharmacological targets for the treatment of chronic progressive MS, the mechanisms of the underlying neurodegenerative process that becomes apparent as the disease progresses need to be elucidated. New animal models with prominent and widespread progressive degenerative components of MS have to be established to study both inflammatory and non-inflammatory mechanisms of neurodegeneration. Here, we discuss disease mechanisms and treatment strategies for chronic progressive MS.ERC; EMB
Chronic Progressive Multiple Sclerosis - Pathogenesis of Neurodegeneration and Therapeutic Strategies
No full textMultiple sclerosis (MS) is an inflammatory, autoimmune, demyelinating disease of the central nervous system (CNS) that usually starts as a relapsing-remitting disease. In most patients the disease evolves into a chronic progressive phase characterized by continuous accumulation of neurological deficits. While treatment of relapsing-remitting MS (RRMS) has improved dramatically over the last decade, the therapeutic options for chronic progressive MS, both primary and secondary, are still limited. In order to find new pharmacological targets for the treatment of chronic progressive MS, the mechanisms of the underlying neurodegenerative process that becomes apparent as the disease progresses need to be elucidated. New animal models with prominent and widespread progressive degenerative components of MS have to be established to study both inflammatory and non-inflammatory mechanisms of neurodegeneration. Here, we discuss disease mechanisms and treatment strategies for chronic progressive MS.ERC; EMB
Reparative inflammation in multiple sclerosis
Full text linkMultiple sclerosis is a chronic inflammatory disease, in which repeated episodes of acute auto-inflammatory attacks trigger demyelinating injury in the central nervous system. Whereas our understanding of the disease-causing immune activation is constantly increasing, much less is known about the injury-induced reparative innate immune responses. Here, we discuss the essential function of microglia and monocyte-derived macrophages in orchestrating debris clearance and regeneration. Dampening reparative inflammation can result in insufficient clearance and, thus, to persisting damage, with the consequences of prolonged inflammation. Thus, an understanding of the entire spectrum of inflammatory responses is essential for the prevention of injury-inducing and the stimulation of repair promoting functions of the immune system
Myelination at a glance
No full textThe myelin sheath is a plasma membrane extension that is laid down in regularly spaced segments along axons of the nervous system. This process involves extensive changes in oligodendrocyte cell shape and membrane architecture. In this Cell Science at a Glance article and accompanying poster, we provide a model of how myelin of the central nervous system is wrapped around axons to form a tightly compacted, multilayered membrane structure. This model may not only explain how myelin is generated during brain development, but could also help us to understand myelin remodeling in adult life, which might serve as a form of plasticity for the fine-tuning of neuronal networks
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