Autoreactive lymphocytes in multiple sclerosis: Pathogenesis and treatment target

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 23, 2022

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by destruction myelin sheath structure. The loss leads to damage neuron’s axon and cell body, which identified as brain lesions on magnetic resonance image (MRI). pathogenesis MS remains largely unknown. However, immune mechanisms, especially those linked aberrant lymphocyte activity, are mainly responsible for neuronal damage. Th1 Th17 populations lymphocytes were primarily associated with pathogenesis. These essential differentiation encephalitogenic CD8 + T crossing blood barrier targeting in CNS. B-lymphocytes could also contribute producing anti-myelin basic protein antibodies. In later studies, function Treg Th9 cells was contributing MS. This review summarizes count lymphocyte, contributions these mechanisms Additionally, we have outlined novel therapeutics aimed amend or counts lymphocytes.

Language: Английский

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A Bioinspired Injectable, Adhesive, and Self‐Healing Hydrogel with Dual Hybrid Network for Neural Regeneration after Spinal Cord Injury

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(41)

Published: July 18, 2023

Hydrogel-based regenerated scaffolds show promise as a platform for neural regeneration following spinal cord injury (SCI). Nevertheless, the persistent problem of poor mechanical strength and limited integration with host tissue still exists. In this study, bioinspired hydrogel highly sophisticated features after SCI is developed. The composed dihydroxyphenylalanine (DOPA)-grafted chitosan designer peptide, offering unique set qualities such being injectable, having self-healing abilities, adhering to tissues. Compared conventional hydrogels, ensures significant promotion immune response modulation axon regrowth while featuring synapse formation various neurotransmitters myelin regeneration. Subsequently, functional recoveries are enhanced, including motor function, sensory particularly bladder defect repair. These positive findings demonstrate that has great potential strategy repairing SCI. Moreover, versatility goes beyond holds in other contexts. Overall, proposed represents an innovative multifaceted tool engineering structures biomedical field.

Language: Английский

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ACSL4-Mediated Ferroptosis and Its Potential Role in Central Nervous System Diseases and Injuries

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(12), P. 10021 - 10021

Published: June 12, 2023

As an iron-dependent regulated form of cell death, ferroptosis is characterized by lipid peroxidation and has been implicated in the occurrence development various diseases, including nervous system diseases injuries. Ferroptosis become a potential target for intervention these or injuries relevant preclinical models. member Acyl-CoA synthetase long-chain family (ACSLs) that can convert saturated unsaturated fatty acids, Acyl—CoA familymember4 (ACSL4) involved regulation arachidonic acid eicosapentaenoic acid, thus leading to ferroptosis. The underlying molecular mechanisms ACSL4-mediated will promote additional treatment strategies injury conditions. Our review article provides current view ferroptosis, mainly structure function ACSL4, as well role ACSL4 We also summarize latest research progress central further proving ACSL4-medicated important

Language: Английский

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Oligodendrocyte death initiates synchronous remyelination to restore cortical myelin patterns in mice

Nature Neuroscience, Journal Year: 2023, Volume and Issue: 26(4), P. 555 - 569

Published: March 16, 2023

Language: Английский

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Lactate Metabolism, Signaling, and Function in Brain Development, Synaptic Plasticity, Angiogenesis, and Neurodegenerative Diseases

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(17), P. 13398 - 13398

Published: Aug. 29, 2023

Neural tissue requires a great metabolic demand despite negligible intrinsic energy stores. As result, the central nervous system (CNS) depends upon continuous influx of substrates from blood. Disruption this process can lead to impairment neurological functions, loss consciousness, and coma within minutes. Intricate neurovascular networks permit both spatially temporally appropriate substrate delivery. Lactate is end product anaerobic or aerobic glycolysis, converted pyruvate by lactate dehydrogenase-5 (LDH-5). Although abundant in brain, it was traditionally considered byproduct waste glycolysis. However, recent evidence indicates may be an important source as well signaling molecule for brain astrocytes—the most glial cell—playing crucial role delivery, storage, production, utilization. The astrocyte–neuron lactate-shuttle hypothesis states that lactate, once released into extracellular space astrocytes, up-taken metabolized neurons. This review focuses on hypothesis, highlighting lactate’s emerging with particular emphasis its during development, synaptic plasticity, angiogenesis, disease.

Language: Английский

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Role of pyroptosis in the pathogenesis of various neurological diseases

Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: 117, P. 428 - 446

Published: Feb. 7, 2024

Language: Английский

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Glial cell alterations in diabetes-induced neurodegeneration

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: Jan. 18, 2024

Abstract Type 2 diabetes mellitus is a global epidemic that due to its increasing prevalence worldwide will likely become the most common debilitating health condition. Even if primarily metabolic disorder, it now well established key aspects of pathogenesis are associated with nervous system alterations, including deleterious chronic inflammation neural tissues, referred here as neuroinflammation, along different detrimental glial cell responses stress conditions and neurodegenerative features. Moreover, resembles accelerated aging, further risk developing age-linked disorders. As such, disabling diabetic comorbidities, namely retinopathy, peripheral neuropathy, cognitive decline, intimately neurodegeneration. described in aging other neurological disorders, alterations such microglial, astrocyte, Müller increased reactivity dysfunctionality, myelin loss Schwann have been broadly both human animal models, where they contributors noxious tissues within PNS CNS. In this review, we aim describe in-depth unique underlying changes observed across three main complications, goal uncovering shared cells pathological mechanisms enable discovery potential targets limit neuroinflammation prevent neurodegeneration all complications. Diabetes complications already public concern rapidly incidence, thus economic impact. Hence, understanding role play decline provide us novel therapeutic approaches tackle diabetic-associated Graphical abstract

Language: Английский

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Oligodendrocytes: Myelination, Plasticity, and Axonal Support

Cold Spring Harbor Perspectives in Biology, Journal Year: 2024, Volume and Issue: 16(10), P. a041359 - a041359

Published: April 15, 2024

Mikael Simons1,2, Erin M. Gibson3 and Klaus-Armin Nave4 1Institute of Neuronal Cell Biology, Technical University Munich, Munich 80802, Germany 2German Center for Neurodegenerative Diseases, Cluster Systems Neurology (SyNergy), Institute Stroke Dementia Research, 81377, 3Department Psychiatry Behavioral Sciences, Stanford School Medicine, 94305, California, USA 4Department Neurogenetics, Max Planck Multidisciplinary Göttingen 37075, Correspondence: mikael.simons{at}dzne.de; egibson1{at}stanford.edu; nave{at}mpinat.mpg.de

Language: Английский

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Oligodendrocyte calcium signaling promotes actin-dependent myelin sheath extension

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 4, 2024

Abstract Myelin is essential for rapid nerve signaling and increasingly found to play important roles in learning diverse diseases of the CNS. Morphological parameters myelin such as sheath length are thought precisely tune conduction velocity, but mechanisms controlling morphology poorly understood. Local calcium has been observed nascent sheaths can be modulated by neuronal activity. However, role formation remains incompletely Here, we use genetic tools attenuate oligodendrocyte during myelination developing mouse Surprisingly, attenuation does not grossly affect number myelinated axons or thickness. Instead, causes defects resulting shorter, dysmorphic sheaths. Mechanistically, reduces actin filaments oligodendrocytes, an intact cytoskeleton necessary sufficient achieve accurate morphology. Together, our work reveals a cellular mechanism required CNS may provide mechanistic insight into how oligodendrocytes respond activity sculpt refine

Language: Английский

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Prolonged myelin deficits contribute to neuron loss and functional impairments after ischaemic stroke

Brain, Journal Year: 2024, Volume and Issue: 147(4), P. 1294 - 1311

Published: Jan. 30, 2024

Abstract Ischaemic stroke causes neuron loss and long-term functional deficits. Unfortunately, effective approaches to preserving neurons promoting recovery remain unavailable. Oligodendrocytes, the myelinating cells in CNS, are susceptible oxygen nutrition deprivation undergo degeneration after ischaemic stroke. Technically, new oligodendrocytes myelin can be generated by differentiation of oligodendrocyte precursor (OPCs). However, dynamics their significance poorly understood. Here, we report numerous denuded axons accompanied decreased density sections from lesions human brain, suggesting that correlates with deficits these lesions. To investigate longitudinal changes stroke, labelled traced pre-existing newly-formed myelin, respectively, using cell-specific genetic approaches. Our results indicated massive death 2 weeks transient middle cerebral artery occlusion (tMCAO) mouse model. In contrast, regeneration remained insufficient 4 8 post-stroke. Notably, neuronal impairments worsened aged brains, generation was diminished. analyse causal relationship between remyelination survival, manipulated myelinogenesis conditional deletion Olig2 (a positive regulator) or muscarinic receptor 1 (M1R, a negative OPCs. Deleting inhibited remyelination, reducing survival tMCAO. Conversely, enhancing M1R knockout treatment pro-myelination drug clemastine tMCAO preserved white matter integrity accelerating recovery. Together, our findings demonstrate is promising strategy preserve promote

Language: Английский

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