scholarly journals The Molecular Basis for Remyelination Failure in Multiple Sclerosis

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 825 ◽  
Author(s):  
Joel Gruchot ◽  
Vivien Weyers ◽  
Peter Göttle ◽  
Moritz Förster ◽  
Hans-Peter Hartung ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Cells ◽  
Brain Function ◽  
Innate Immune ◽  
Adult Brain ◽  
Innate Immune Cells ◽  
Regenerative Capacity ◽  
Myelin Sheaths ◽  
The Central Nervous System ◽  
Inflammatory Autoimmune Disease

Myelin sheaths in the central nervous system (CNS) insulate axons and thereby allow saltatory nerve conduction, which is a prerequisite for complex brain function. Multiple sclerosis (MS), the most common inflammatory autoimmune disease of the CNS, leads to the destruction of myelin sheaths and the myelin-producing oligodendrocytes, thus leaving behind demyelinated axons prone to injury and degeneration. Clinically, this process manifests itself in significant neurological symptoms and disability. Resident oligodendroglial precursor cells (OPCs) and neural stem cells (NSCs) are present in the adult brain, and can differentiate into mature oligodendrocytes which then remyelinate the demyelinated axons. However, for multiple reasons, in MS the regenerative capacity of these cell populations diminishes significantly over time, ultimately leading to neurodegeneration, which currently remains untreatable. In addition, microglial cells, the resident innate immune cells of the CNS, can contribute further to inflammatory and degenerative axonal damage. Here, we review the molecular factors contributing to remyelination failure in MS by inhibiting OPC and NSC differentiation or modulating microglial behavior.

scholarly journals Microglia in Alzheimer's Disease: It's All About Context

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Tara M. Weitz ◽  
Terrence Town
Keyword(s):  
Immune Cells ◽  
Innate Immune ◽  
Brain Inflammation ◽  
Early Event ◽  
Innate Immune Cells ◽  
Prime Mover ◽  
Reactive Microglia ◽  
Future Studies ◽  
Immunological Responses ◽  
The Central Nervous System

Neuroinflammation is now regarded as both an early event and prime mover in the pathobiology of Alzheimer disease (AD), a neurodegenerative disease that represents a growing public health threat. As the resident innate immune cells within the central nervous system, microglia are centrally positioned as key orchestrators of brain inflammation. It is now accepted that numerous forms of activated microglia exist. Furthermore, while some types of reactive microglia are detrimental, others can actually be beneficial. In the context of AD etiopathology, much debate surrounds whether these enigmatic cells play “good” or “bad” roles. In this article, we distill a complex clinical and experimental literature focused on the contribution of microglia to AD pathology and progression. A synthesis of the literature only seems possible when considering context– the conditions under which microglia encounter and mount immunological responses to AD pathology. In order to carry out these diverse contextual responses, a number of key receptors and signaling pathways are variously activated. It will be critically important for future studies to address molecular mediators that lead to beneficial microglial responses and therefore represent important therapeutic targets for AD.

scholarly journals Alemtuzumab treatment alters circulating innate immune cells in multiple sclerosis

2016 ◽  
Vol 3 (6) ◽  
pp. e289 ◽  
Author(s):  
Catharina C. Gross ◽  
Diana Ahmetspahic ◽  
Tobias Ruck ◽  
Andreas Schulte-Mecklenbeck ◽  
Kathrin Schwarte ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Cells ◽  
Innate Immune ◽  
Innate Immune Cells

scholarly journals Triggering Innate Immune Receptors as New Therapies in Alzheimer’s Disease and Multiple Sclerosis

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2164
Author(s):  
Pierre-Alexandre Piec ◽  
Vincent Pons ◽  
Serge Rivest
Keyword(s):  
Multiple Sclerosis ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Innate Immunity ◽  
Immune Cells ◽  
Therapeutic Potential ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Disease Course ◽  
Beneficial Effects

Multiple sclerosis and Alzheimer’s disease are two complex neurodegenerative diseases involving the immune system. So far, available treatments provide at best mild improvements to patients’ conditions. For decades now, a new set of molecules have been used to modulate and regulate the innate immunity in these pathologies. Most studies have been carried out in rodents and some of them have reported tremendous beneficial effects on the disease course. The modulation of innate immune cells is of great interest since it provides new hope for patients. In this review, we will briefly overview the therapeutic potential of some molecules and receptors in multiple sclerosis and Alzheimer’s disease and how they could be used to exploit new therapeutic avenues.

scholarly journals In vivo nanoparticle imaging of innate immune cells can serve as a marker of disease severity in a model of multiple sclerosis

2016 ◽  
Vol 113 (46) ◽  
pp. 13227-13232 ◽  
Author(s):  
Klara Kirschbaum ◽  
Jana K. Sonner ◽  
Matthias W. Zeller ◽  
Katrin Deumelandt ◽  
Julia Bode ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Iron Oxide ◽  
Molecular Imaging ◽  
Immune Cells ◽  
Innate Immune ◽  
Iron Oxide Nanoparticle ◽  
Innate Immune Cells ◽  
Nanoparticle Imaging ◽  
Oxide Nanoparticle

Innate immune cells play a key role in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Current clinical imaging is restricted to visualizing secondary effects of inflammation, such as gliosis and blood–brain barrier disruption. Advanced molecular imaging, such as iron oxide nanoparticle imaging, can allow direct imaging of cellular and molecular activity, but the exact cell types that phagocytose nanoparticles in vivo and how phagocytic activity relates to disease severity is not well understood. In this study we used MRI to map inflammatory infiltrates using high-field MRI and fluorescently labeled cross-linked iron oxide nanoparticles for cell tracking. We confirmed nanoparticle uptake and MR detectability ex vivo. Using in vivo MRI, we identified extensive nanoparticle signal in the cerebellar white matter and circumscribed cortical gray matter lesions that developed during the disease course (4.6-fold increase of nanoparticle accumulation in EAE compared with healthy controls, P < 0.001). Nanoparticles showed good cellular specificity for innate immune cells in vivo, labeling activated microglia, infiltrating macrophages, and neutrophils, whereas there was only sparse uptake by adaptive immune cells. Importantly, nanoparticle signal correlated better with clinical disease than conventional gadolinium (Gd) imaging (r, 0.83 for nanoparticles vs. 0.71 for Gd-imaging, P < 0.001). We validated our approach using the Food and Drug Administration-approved iron oxide nanoparticle ferumoxytol. Our results show that noninvasive molecular imaging of innate immune responses can serve as an imaging biomarker of disease activity in autoimmune-mediated neuroinflammation with potential clinical applications in a wide range of inflammatory diseases.

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