Targeting Fibronectin to Overcome Remyelination Failure in Multiple Sclerosis: The Need for Brain- and Lesion-Targeted Drug Delivery

Schaik, Pauline E. M. van; Zuhorn, Inge S.; Baron, Wia

doi:10.3390/ijms23158418

Cited by 10 publications

(9 citation statements)

References 394 publications

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“…In addition, there was a considerable upregulation ( p < 0.05) of the fibronectin and PDGF genes. Fibronectin and PDGF are essential in improving wound repair and inducing tissue regeneration [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Silver Nanoparticles Prepared Using Encephalartos laurentianus De Wild Leaf Extract Have Inhibitory Activity against Candida albicans Clinical Isolates

Alherz

Negm

Elekhnawy

et al. 2022

JoF

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Candida albicans is a major human opportunistic pathogen causing infections, which range from cutaneous to invasive systemic infections. Herein, the antifungal and anti-biofilm potential of silver nanoparticles (AgNPs) green synthesized in the presence of Encephalartos laurentianus leaf extract (ELLE) were investigated. The bioactive chemicals of ELLE, including phenolics, flavonoids, and glycosides were identified and quantified for the first time. AgNPs showed minimum inhibitory concentration (MIC) values against C. albicans clinical isolates ranging from 8 to 256 µg/mL. In addition, AgNPs significantly decreased biofilm formation. The impact of AgNPs on the expression of the genes encoding biofilm formation was assessed using qRT-PCR. AgNPs had a beneficial role in the macroscopic wound healing, and they resulted in complete epithelization without any granulation tissue or inflammation. Treatment with AgNPs resulted in negative immunostaining of tumor necrosis factor-α. The levels of the inflammation markers, interleukin-6 and interleukin-1β, significantly decreased (p < 0.05) in the AgNPs-treated group. There was also a pronounced increase in the gene expression of fibronectin and platelet-derived growth factor in the wound tissues. Thus, AgNPs synthesized using ELLE may be a promising antifungal and wound healing agent.

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Section: Discussionmentioning

confidence: 99%

Silver Nanoparticles Prepared Using Encephalartos laurentianus De Wild Leaf Extract Have Inhibitory Activity against Candida albicans Clinical Isolates

Alherz

Negm

Elekhnawy

et al. 2022

JoF

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“…Several genes that increased their expression in the hippocampus and partially in the cortex of OBX mice are of particular interest. They are represented by the Ywhag gene encoding 14-3-3γ protein, which increased GSK-3β activation and promoted tau phosphorylation in Alzheimer's disease [50], Fn1 -bronectin1, which declined at the onset of remyelination of the lesion area of the CNS and is implicated in BBB breakdown [51]. All studied brain structures of OBX mice were characterized by a pronounced increase in the level of expression of the Sox9 gene, which responds to Aβ deposition [52].…”

Section: Study Of Gene Expression In the Brain Regions Of Obx Mice Re...mentioning

confidence: 99%

A mouse model of sporadic Alzheimer’s disease with elements of major depression

Bobkova,

Chuvakova,

Kovalev

et al. 2024

Preprint

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Animals after bulbectomy are often used as a model of major depression or sporadicAlzheimer’s disease and, hence, the status of this model is still disputable. To elucidate the nature of alterations in the expression of the genome after the operation we analyzed transcriptomes (RNA-seq data) of the cortex, hippocampus, and cerebellum of olfactory bulbectomized (OBX) mice. Analysis of the functional significance of genes in the brain of OBX mice indicates that the balance of the GABA/glutamatergic systems is disturbed with hyperactivation of the latter in the hippocampus leading to the development of excitotoxicity and induction of apoptosis on the background of severe mitochondrial dysfunction and astrogliosis. On top of this, the synthesis of neurotrophic factors decreases leading to the disruption of the cytoskeleton of neurons, an increase in the level of intracellular calcium, and activation of tau protein hyperphosphorylation and beta-amyloid depositions. Moreover, the acetylcholinergic system is deficient in the background of hyperactivation of acetylcholinesterase. Importantly, the activity of the dopaminergic, endorphin, and opiate systems in OBX mice decreases leading to hormonal dysfunction. Genes responsible for the regulation of circadian rhythms, cell migration, and impaired innate immunity are activated in OBX animals. All this takes place on the background of drastic down-regulation of ribosomal protein genes in the brain. The obtained results indicate that OBX mice represent a model of Alzheimer's disease with elements of major depression. This model can be tentatively attributed to AD subtype B2 in humans.

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“…Given the consensus that inflammation drives demyelination in MS patients, most of the current therapies rely on immune-modulating strategies that either dampen the overall activity of the immune system or block the entry of peripheral immune cells into the CNS [ 4 ]. However, these therapies often fail in patients with progressive MS [ 5 ], where chronic demyelination and neuroaxonal loss are the key to irreversible neurological disability [ 6 , 7 ]. Although natural partial remyelination can be detected in a small percentage of patients post-mortem, it is neither efficient nor sufficient to halt axonal atrophy and loss [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Impact of the Voltage-Gated Calcium Channel Antagonist Nimodipine on the Development of Oligodendrocyte Precursor Cells

Enders

Weier

Chunder

et al. 2023

IJMS

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Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). While most of the current treatment strategies focus on immune cell regulation, except for the drug siponimod, there is no therapeutic intervention that primarily aims at neuroprotection and remyelination. Recently, nimodipine showed a beneficial and remyelinating effect in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Nimodipine also positively affected astrocytes, neurons, and mature oligodendrocytes. Here we investigated the effects of nimodipine, an L-type voltage-gated calcium channel antagonist, on the expression profile of myelin genes and proteins in the oligodendrocyte precursor cell (OPC) line Oli-Neu and in primary OPCs. Our data indicate that nimodipine does not have any effect on myelin-related gene and protein expression. Furthermore, nimodipine treatment did not result in any morphological changes in these cells. However, RNA sequencing and bioinformatic analyses identified potential micro (mi)RNA that could support myelination after nimodipine treatment compared to a dimethyl sulfoxide (DMSO) control. Additionally, we treated zebrafish with nimodipine and observed a significant increase in the number of mature oligodendrocytes (* p≤ 0.05). Taken together, nimodipine seems to have different positive effects on OPCs and mature oligodendrocytes.

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Targeting Fibronectin to Overcome Remyelination Failure in Multiple Sclerosis: The Need for Brain- and Lesion-Targeted Drug Delivery

Cited by 10 publications

References 394 publications

Silver Nanoparticles Prepared Using Encephalartos laurentianus De Wild Leaf Extract Have Inhibitory Activity against Candida albicans Clinical Isolates

Silver Nanoparticles Prepared Using Encephalartos laurentianus De Wild Leaf Extract Have Inhibitory Activity against Candida albicans Clinical Isolates

A mouse model of sporadic Alzheimer’s disease with elements of major depression

Impact of the Voltage-Gated Calcium Channel Antagonist Nimodipine on the Development of Oligodendrocyte Precursor Cells

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