The Role of Complement C3a Receptor in Stroke

Ahmad, Saif; Bhatia, Kanchan; Kindelin, Adam; Ducruet, Andrew F.

doi:10.1007/s12017-019-08545-7

Cited by 12 publications

(8 citation statements)

References 68 publications

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“…Evidence suggests that complement C3 is central to stroke pathology in animal models [234]. MCAO resulted in a significant increase in mRNA of C3a and C5a receptors on the ipsilateral side [35], and reports have shown that C3aR and C5aR1 mRNA peaked at 24-48 h after injury [35,235].…”

Section: Strokementioning

confidence: 98%

The good, the bad, and the opportunities of the complement system in neurodegenerative disease

Schartz

Tenner

2020

J Neuroinflammation

152

183

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The complement cascade is a critical effector mechanism of the innate immune system that contributes to the rapid clearance of pathogens and dead or dying cells, as well as contributing to the extent and limit of the inflammatory immune response. In addition, some of the early components of this cascade have been clearly shown to play a beneficial role in synapse elimination during the development of the nervous system, although excessive complement-mediated synaptic pruning in the adult or injured brain may be detrimental in multiple neurogenerative disorders. While many of these later studies have been in mouse models, observations consistent with this notion have been reported in human postmortem examination of brain tissue. Increasing awareness of distinct roles of C1q, the initial recognition component of the classical complement pathway, that are independent of the rest of the complement cascade, as well as the relationship with other signaling pathways of inflammation (in the periphery as well as the central nervous system), highlights the need for a thorough understanding of these molecular entities and pathways to facilitate successful therapeutic design, including target identification, disease stage for treatment, and delivery in specific neurologic disorders. Here, we review the evidence for both beneficial and detrimental effects of complement components and activation products in multiple neurodegenerative disorders. Evidence for requisite co-factors for the diverse consequences are reviewed, as well as the recent studies that support the possibility of successful pharmacological approaches to suppress excessive and detrimental complement-mediated chronic inflammation, while preserving beneficial effects of complement components, to slow the progression of neurodegenerative disease.

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Section: Strokementioning

confidence: 98%

The good, the bad, and the opportunities of the complement system in neurodegenerative disease

Schartz

Tenner

2020

J Neuroinflammation

152

183

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“… 70 , 71 On the other hand, after stroke, generation of C3a also contributes to the recovery of ischemic tissue by promoting regeneration and the resolution of inflammation. 72 This double-edge sword translates into a challenging task (or opportunity) for targeting complement mediators as a possible therapeutic strategy for this disorder. 73 However, as it is clear that deposition of C3b and thus the subsequent formation of C3 and C5 convertases is a central event in stroke pathology, numerous studies have used C3 as their main target to treat stroke.…”

Section: Complement In the Brainmentioning

confidence: 99%

The Role of Complement in Synaptic Pruning and Neurodegeneration

Gómez-Arboledas

Acharya

Tenner

2021

ITT

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The complement system, an essential part of the innate immune system, is composed of a group of secreted and membrane proteins that collectively participate in maintaining the function of the healthy and diseased brain. However, an inappropriate activation of the complement system has been related to an inflammatory response in multiple diseases, such as stroke, traumatic brain injury, multiple sclerosis, and Alzheimer’s disease, as well as Zika infection and radiotherapy. In addition, C1q and C3 (initial activation components of the complement cascade) have been shown to play a key beneficial role in the refinement of synaptic circuits during developmental stages and adult plasticity. Nevertheless, excessive synaptic pruning in the adult brain can be detrimental and has been associated with synaptic loss in several pathological conditions. In this brief review, we will discuss the role of the complement system in synaptic pruning as well as its contribution to neurodegeneration and cognitive deficits. We also mention potential therapeutic approaches to target the complement system to treat several neuroinflammatory diseases and unintended consequences of radiotherapy.

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“…Of note is also the marked up-regulation of the complement factor C3 belonging to a complex network of plasma and membrane proteins involved in the innate immunity [74]. Complement can modulate the inflammatory response during wound healing to restore tissue injury; however, its unbalanced or prolonged activation can exacerbate inflammation, delaying the physiological wound healing [75].…”

Section: Altered Ecm Turnover Wound Healing and Inflammation In mentioning

confidence: 99%

Cellular and Molecular Mechanisms in the Pathogenesis of Classical, Vascular, and Hypermobile Ehlers‒Danlos Syndromes

Chiarelli

Ritelli

Zoppi

et al. 2019

Genes

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The Ehlers‒Danlos syndromes (EDS) constitute a heterogenous group of connective tissue disorders characterized by joint hypermobility, skin abnormalities, and vascular fragility. The latest nosology recognizes 13 types caused by pathogenic variants in genes encoding collagens and other molecules involved in collagen processing and extracellular matrix (ECM) biology. Classical (cEDS), vascular (vEDS), and hypermobile (hEDS) EDS are the most frequent types. cEDS and vEDS are caused respectively by defects in collagen V and collagen III, whereas the molecular basis of hEDS is unknown. For these disorders, the molecular pathology remains poorly studied. Herein, we review, expand, and compare our previous transcriptome and protein studies on dermal fibroblasts from cEDS, vEDS, and hEDS patients, offering insights and perspectives in their molecular mechanisms. These cells, though sharing a pathological ECM remodeling, show differences in the underlying pathomechanisms. In cEDS and vEDS fibroblasts, key processes such as collagen biosynthesis/processing, protein folding quality control, endoplasmic reticulum homeostasis, autophagy, and wound healing are perturbed. In hEDS cells, gene expression changes related to cell-matrix interactions, inflammatory/pain responses, and acquisition of an in vitro pro-inflammatory myofibroblast-like phenotype may contribute to the complex pathogenesis of the disorder. Finally, emerging findings from miRNA profiling of hEDS fibroblasts are discussed to add some novel biological aspects about hEDS etiopathogenesis.

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The Role of Complement C3a Receptor in Stroke

Cited by 12 publications

References 68 publications

The good, the bad, and the opportunities of the complement system in neurodegenerative disease

The good, the bad, and the opportunities of the complement system in neurodegenerative disease

The Role of Complement in Synaptic Pruning and Neurodegeneration

Cellular and Molecular Mechanisms in the Pathogenesis of Classical, Vascular, and Hypermobile Ehlers‒Danlos Syndromes

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