The Impact of the CX3CL1/CX3CR1 Axis in Neurological Disorders

Pawelec, Paulina; Ziemka‐Nałęcz, Małgorzata; Sypecka, Joanna; Zalewska, Teresa

doi:10.3390/cells9102277

Cited by 157 publications

(131 citation statements)

References 128 publications

Supporting

Mentioning

116

Contrasting

Order By: Relevance

“…Several studies have shown its role in the epilepsy pathogenesis and concomitant cell death. Blocking of CX3CL1/CX3CR1 signaling pathway by antibodies reduces microglial activation and neurodegeneration caused by an electrical epileptic seizure in rodents [43].…”

Section: Chemokines Fractalkin (Fkn Cx3cl1)mentioning

confidence: 99%

Mechanisms of Drug Resistance in the Pathogenesis of Epilepsy: Role of Neuroinflammation. A Literature Review

2021

View full text Add to dashboard Cite

Epilepsy is a chronic neurological disorder characterized by recurring spontaneous seizures. Drug resistance appears in 30% of patients and it can lead to premature death, brain damage or a reduced quality of life. The purpose of the study was to analyze the drug resistance mechanisms, especially neuroinflammation, in the epileptogenesis. The information bases of biomedical literature Scopus, PubMed, Google Scholar and SciVerse were used. To obtain full-text documents, electronic resources of PubMed Central and Research Gate were used. The article examines the recent research of the mechanisms of drug resistance in epilepsy and discusses the hypotheses of drug resistance development (genetic, epigenetic, target hypothesis, etc.). Drug-resistant epilepsy is associated with neuroinflammatory, autoimmune and neurodegenerative processes. Neuroinflammation causes immune, pathophysiological, biochemical and psychological consequences. Focal or systemic unregulated inflammatory processes lead to the formation of aberrant neural connections and hyperexcitable neural networks. Inflammatory mediators affect the endothelium of cerebral vessels, destroy contacts between endothelial cells and induce abnormal angiogenesis (the formation of “leaky” vessels), thereby affecting the blood–brain barrier permeability. Thus, the analysis of pro-inflammatory and other components of epileptogenesis can contribute to the further development of the therapeutic treatment of drug-resistant epilepsy.

show abstract

Section: Chemokines Fractalkin (Fkn Cx3cl1)mentioning

confidence: 99%

Mechanisms of Drug Resistance in the Pathogenesis of Epilepsy: Role of Neuroinflammation. A Literature Review

2021

View full text Add to dashboard Cite

show abstract

“…CX3CL1 (Fractalkine) is a ligand for chemokine receptor CX3CR1. Multiple lines of evidence suggest that CX3CL1/CX3CR1 axis plays important roles in the neuropathology of various brain disorders such as cerebral ischemia, epilepsy, and AD (Reviewed in Pawelec et al, 2020). Bolos et al (2017) reported that CX3CR1 deficiency decreases the internalization of 2N4R tau monomer in microglia both in vitro and in vivo.…”

Section: The Interaction Of Tau With Membrane Proteinsmentioning

confidence: 99%

Role of the Lipid Membrane and Membrane Proteins in Tau Pathology

Bok

Leem

Lee

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Abnormal accumulation of misfolded tau aggregates is a pathological hallmark of various tauopathies including Alzheimer’s disease (AD). Although tau is a cytosolic microtubule-associated protein enriched in neurons, it is also found in extracellular milieu, such as interstitial fluid, cerebrospinal fluid, and blood. Accumulating evidence showed that pathological tau spreads along anatomically connected areas in the brain through intercellular transmission and templated misfolding, thereby inducing neurodegeneration and cognitive dysfunction. In line with this, the spatiotemporal spreading of tau pathology is closely correlated with cognitive decline in AD patients. Although the secretion and uptake of tau involve multiple different pathways depending on tau species and cell types, a growing body of evidence suggested that tau is largely secreted in a vesicle-free forms. In this regard, the interaction of vesicle-free tau with membrane is gaining growing attention due to its importance for both of tau secretion and uptake as well as aggregation. Here, we review the recent literature on the mechanisms of the tau-membrane interaction and highlights the roles of lipids and proteins at the membrane in the tau-membrane interaction as well as tau aggregation.

show abstract

“…Specific presynaptic (SNAP25) and postsynaptic (PSD95) proteins were identified inside microglial processes following synaptic contacts, by confocal or immune-gold electron microscopy, respectively ( 18 ). Furthermore, disrupting the fractalkine (Cx3cl1/Cx3cr1)-mediated communication between microglia and neurons in an otherwise healthy mouse, resulted in brain circuits persisting as immature into adulthood ( 18 , 180 , 181 ). In 2012, the Stevens' lab at Boston Children's Hospital, found that, in the newborn mouse visual system, microglia can engulf synapses in the lateral geniculate nucleus (LGN) through a process mediated by both complement and neuronal activity.…”

Section: Experimental Settings For Investigating Synapse Elimination mentioning

confidence: 99%

Strategies and Tools for Studying Microglial-Mediated Synapse Elimination and Refinement

et al. 2021

View full text Add to dashboard Cite

The role of microglia in controlling synapse homeostasis is becoming increasingly recognized by the scientific community. In particular, the microglia-mediated elimination of supernumerary synapses during development lays the basis for the correct formation of neuronal circuits in adulthood, while the possible reactivation of this process in pathological conditions, such as schizophrenia or Alzheimer's Disease, provides a promising target for future therapeutic strategies. The methodological approaches to investigate microglial synaptic engulfment include different in vitro and in vivo settings. Basic in vitro assays, employing isolated microglia and microbeads, apoptotic membranes, liposomes or synaptosomes allow the quantification of the microglia phagocytic abilities, while co-cultures of microglia and neurons, deriving from either WT or genetically modified mice models, provide a relatively manageable setting to investigate the involvement of specific molecular pathways. Further detailed analysis in mice brain is then mandatory to validate the in vitro assays as representative for the in vivo situation. The present review aims to dissect the main technical approaches to investigate microglia-mediated phagocytosis of neuronal and synaptic substrates in critical developmental time windows.

show abstract

The Impact of the CX3CL1/CX3CR1 Axis in Neurological Disorders

Cited by 157 publications

References 128 publications

Mechanisms of Drug Resistance in the Pathogenesis of Epilepsy: Role of Neuroinflammation. A Literature Review

Mechanisms of Drug Resistance in the Pathogenesis of Epilepsy: Role of Neuroinflammation. A Literature Review

Role of the Lipid Membrane and Membrane Proteins in Tau Pathology

Strategies and Tools for Studying Microglial-Mediated Synapse Elimination and Refinement

Contact Info

Product

Resources

About