Neurol Neuroimmunol Neuroinflamm
November 2024
We introduce a novel tree-based method for visualizing molecular conformation sampling. Our method offers enhanced precision in highlighting conformational differences and facilitates the observation of local minimas within proteins fold space. The projection of empirical laboratory data on the tree allows us to create a link between protein conformations and disease relevant data.
View Article and Find Full Text PDFIdentifying the nodes able to drive the state of a network is crucial to understand, and eventually control, biological systems. Despite recent advances, such identification remains difficult because of the huge number of equivalent controllable configurations, even in relatively simple networks. Based on the evidence that in many applications it is essential to test the ability of individual nodes to control a specific target subset, we develop a fast and principled method to identify controllable driver-target configurations in sparse and directed networks.
View Article and Find Full Text PDFMultiple sclerosis (MS) is a neuroinflammatory disease whose pathogenesis remains unclear. Lysophosphatidic acid (LPA) is an endogenous phospholipid involved in multiple immune cell functions and dysregulated in MS. Its receptor LPA is expressed in macrophages and regulates their activation, which is of interest due to the role of macrophage activation in MS in both destruction and repair.
View Article and Find Full Text PDFSchwann cells (SC) enter the central nervous system (CNS) in pathophysiological conditions. However, how SC invade the CNS to remyelinate central axons remains undetermined. We studied SC migratory behavior ex vivo and in vivo after exogenous transplantation in the demyelinated spinal cord.
View Article and Find Full Text PDFRemyelination of CNS axons by Schwann cells (SCs) is not efficient, in part due to the poor migration of SCs into the adult CNS. Although it is known that migrating SCs avoid white matter tracts, the molecular mechanisms underlying this exclusion have never been elucidated. We now demonstrate that myelin-associated glycoprotein (MAG), a well known inhibitor of neurite outgrowth, inhibits rat SC migration and induces their death via γ-secretase-dependent regulated intramembrane proteolysis of the p75 neurotrophin receptor (also known as p75 cleavage).
View Article and Find Full Text PDFOne major challenge in multiple sclerosis is to understand the cellular and molecular mechanisms leading to disease severity progression. The recently demonstrated correlation between disease severity and remyelination emphasizes the importance of identifying factors leading to a favourable outcome. Why remyelination fails or succeeds in multiple sclerosis patients remains largely unknown, mainly because remyelination has never been studied within a humanized pathological context that would recapitulate major events in plaque formation such as infiltration of inflammatory cells.
View Article and Find Full Text PDFPelizaeus-Merzbacher disease (PMD) results from an X-linked misexpression of proteolipid protein 1 (PLP1). This leukodystrophy causes severe hypomyelination with progressive inflammation, leading to neurological dysfunctions and shortened life expectancy. While no cure exists for PMD, experimental cell-based therapy in the dysmyelinated shiverer model suggested that human oligodendrocyte progenitor cells (hOPCs) or human neural precursor cells (hNPCs) are promising candidates to treat myelinopathies.
View Article and Find Full Text PDFIt has been proposed that the adult dorsal root ganglia (DRG) harbor neural stem/progenitor cells (NPCs) derived from the neural crest. However, the thorough characterization of their stemness and differentiation plasticity was not addressed. In this study, we investigated adult DRG-NPC stem cell properties overtime, and their fate when ectopically grafted in the central nervous system.
View Article and Find Full Text PDFSchwann cell (SC) transplantation is currently being discussed as a strategy that may promote functional recovery in patients with multiple sclerosis (MS) and other inflammatory demyelinating diseases of the central nervous system (CNS). However this assumes they will not only survive but also remyelinate demyelinated axons in the chronically inflamed CNS. To address this question we investigated the fate of transplanted SCs in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) in the Dark Agouti rat; an animal model that reproduces the complex inflammatory demyelinating immunopathology of MS.
View Article and Find Full Text PDFBoundary cap cells (BC), which express the transcription factor Krox20, participate in the formation of the boundary between the central nervous system and the peripheral nervous system. To study BC stemness, we developed a method to purify and amplify BC in vitro from Krox20(Cre/+), R26R(YFP/+) mouse embryos. We show that BC progeny are EGF/FGF2-responsive, form spheres, and express neural crest markers.
View Article and Find Full Text PDFThe loss of myelin, a major element involved in the saltatory conduction of the electrical impulse of the nervous system, is a major target of current research. Serious long-term disabilities are observed in patients with demyelinating disease of the central nervous system, such as multiple sclerosis. New therapeutic strategies aimed at overcoming myelin damage and axonal loss focus on the repair potential of myelin-forming cells.
View Article and Find Full Text PDFFacial nerve axotomy (FNA) is a well-established experimental model of motoneuron regeneration. After peripheral nerve axotomy, a sequence of events including glial activation and axonal regrowth leads to functional recovery of the afflicted pool of motoneurons. Using microarray analysis we identified an increase in the expression of 60 genes (at a false discovery rate of 0.
View Article and Find Full Text PDFFractalkine (FKN/CX3CL1) is a cell surface-expressed chemokine involved in many aspects of leukocyte trafficking and activation. The various structural domains of FKN play distinct roles in its ability to bind and activate its receptor, CX3CR1. A human herpesvirus 8-encoded chemokine, termed viral macrophage inflammatory protein (vMIP)-II, is structurally similar to FKN; vMIP-II is a nonselective chemokine receptor antagonist (binding multiple chemokine receptors, including CX3CR1).
View Article and Find Full Text PDFIn order to understand processes involved in central nervous system inflammatory diseases, a critical appreciation of mechanisms involved in the control of immune function in the brain is needed. Microglial cells are watchful eyes for unusual events and detecting the presence of pathogens but are also alert to signals emanating from damaged neurons. Fractalkine (CX3CL1) is a chemokine which is expressed predominantly in the central nervous system, being localized on neurons, while its receptor, CX3CR1, is found on microglial cells.
View Article and Find Full Text PDF