Insight into the roles of CCR5 in learning and memory in normal and disordered states

Necula, Deanna; Riviere-Cazaux, Cecile; Shen, Yang; Zhou, Miou

doi:10.1016/j.bbi.2020.11.037

Cited by 37 publications

(34 citation statements)

References 91 publications

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“…Somatostatin, which is encoded by SST, is a widely distributed peptide in the central nervous system where it affects the rates of neurotransmission, and it was reported to be decreased in cerebrospinal fluid in patients with AD and VaD (Heilig et al, 1995). CCR5 encodes a seven-membrane, G proteincoupled receptor that may impact learning and memory by acting on CREB signaling, a pathway that is critical for learning and memory (Necula et al, 2021). CRH encodes a member of the corticotropin-releasing factor family that functions as a significant regulator of homeostasis, mediating the autonomic, behavioral, and neuroendocrine responses to stress (Dedic et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Identification of Molecular Signatures and Candidate Drugs in Vascular Dementia by Bioinformatics Analyses

Shu

Wei

Zhang

2022

Front. Mol. Neurosci.

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Vascular dementia (VaD) is considered to be the second most common form of dementia after Alzheimer’s disease, and no specific drugs have been approved for VaD treatment. We aimed to identify shared transcriptomic signatures between the frontal cortex and temporal cortex in VaD by bioinformatics analyses. Gene ontology and pathway enrichment analyses, protein–protein interaction (PPI) and hub gene identification, hub gene–transcription factor interaction, hub gene–microRNA interaction, and hub gene–drug interaction analyses were performed. We identified 159 overlapping differentially expressed genes (DEGs) between the frontal cortex and temporal cortex that were enriched mainly in inflammation and innate immunity, synapse pruning, regeneration, positive regulation of angiogenesis, response to nutrient levels, and positive regulation of the digestive system process. We identified 10 hub genes in the PPI network (GNG13, CD163, C1QA, TLR2, SST, C1QB, ITGB2, CCR5, CRH, and TAC1), four central regulatory transcription factors (FOXC1, CREB1, GATA2, and HINFP), and four microRNAs (miR-27a-3p, miR-146a-5p, miR-335-5p, and miR-129-2-3p). Hub gene–drug interaction analysis found four drugs (maraviroc, cenicriviroc, PF-04634817, and efalizumab) that could be potential drugs for VaD treatment. Together, our results may contribute to understanding the underlying mechanisms in VaD and provide potential targets and drugs for therapeutic intervention.

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Section: Discussionmentioning

confidence: 99%

Identification of Molecular Signatures and Candidate Drugs in Vascular Dementia by Bioinformatics Analyses

Shu

Wei

Zhang

2022

Front. Mol. Neurosci.

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“…In the brain, CCR5 is highly expressed in microglia and to a lesser extent in astrocytes, and neurons ( Fantuzzi et al, 2019 ). In AD patients and AD rodent models, increased expression of CCR5 suggests a correlation between AD and CCR5 expression ( Necula et al, 2021 ). CCR5 expression is strongly related to microglia and inflammation, which accelerate the development of AD ( Li and Zhu, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Mechanism and Key Alkaloids of Uncaria rhynchophylla in Alzheimer’s Disease From the Perspective of Pathophysiological Processes

Zeng

Qiu

et al. 2021

Front. Pharmacol.

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Presently, there is a lack of effective disease-modifying drugs for the treatment of Alzheimer’s disease (AD). Uncaria rhynchophylla (UR) and its predominant active phytochemicals alkaloids have been studied to treat AD. This study used a novel network pharmacology strategy to identify UR alkaloids against AD from the perspective of AD pathophysiological processes and identified the key alkaloids for specific pathological process. The analysis identified 10 alkaloids from UR based on high-performance liquid chromatography (HPLC) that corresponded to 127 targets correlated with amyloid-β (Aβ) pathology, tau pathology and Alzheimer disease pathway. Based on the number of targets correlated with AD pathophysiological processes, angustoline, angustidine, corynoxine and isocorynoxeine are highly likely to become key phytochemicals in AD treatment. Among the 127 targets, JUN, STAT3, MAPK3, CCND1, MMP2, MAPK8, GSK3B, JAK3, LCK, CCR5, CDK5 and GRIN2B were identified as core targets. Based on the pathological process of AD, angustoline, angustidine and isocorynoxeine were identified as the key UR alkaloids regulating Aβ production and corynoxine, isocorynoxeine, dihydrocorynatheine, isorhynchophylline and hirsutine were identified as key alkaloids that regulate tau phosphorylation. The findings of this study contribute to a more comprehensive understanding of the key alkaloids and mechanisms of UR in the treatment of AD, as well as provide candidate compounds for drug research and development for specific AD pathological processes.

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“…Another chemokine, CCL3, with its receptor, CCR5, elicited reduced glutamate transmission by a postsynaptic mechanism in the hippocampus [ 87 ]. It should be noted that the potential involvement of glial cells was not investigated in this study despite well-documented astrocytic secretion of CCL5 and CCL3, ligands of CCR5 (for review: [ 88 ]). Thus, further experiments identifying the properties and functions of each of neuronal, microglial, astrocytic and, oligodendrocytic compartments remain to be addressed.…”

Section: Chemokine Action From Synapses To Behaviormentioning

confidence: 99%

“…As described in the section on synaptic plasticity (see “ Hebbian plasticity—LTP and LTD ”), several chemokines were documented to modulate LTP in the hippocampus, a cellular mechanism underlying learning and memory [ 88 , 121 , 143 , 162 ]. Of these chemokines, CX3CL1 is the best characterized in this context.…”

Section: Chemokine Action From Synapses To Behaviormentioning

confidence: 99%

Cellular, synaptic, and network effects of chemokines in the central nervous system and their implications to behavior

Sowa

Tokarski

2021

Pharmacol. Rep

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Accumulating evidence highlights chemokines as key mediators of the bidirectional crosstalk between neurons and glial cells aimed at preserving brain functioning. The multifaceted role of these immune proteins in the CNS is mirrored by the complexity of the mechanisms underlying its biological function, including biased signaling. Neurons, only in concert with glial cells, are essential players in the modulation of brain homeostatic functions. Yet, attempts to dissect these complex multilevel mechanisms underlying coordination are still lacking. Therefore, the purpose of this review is to summarize the current knowledge about mechanisms underlying chemokine regulation of neuron–glia crosstalk linking molecular, cellular, network, and behavioral levels. Following a brief description of molecular mechanisms by which chemokines interact with their receptors and then summarizing cellular patterns of chemokine expression in the CNS, we next delve into the sequence and mechanisms of chemokine-regulated neuron–glia communication in the context of neuroprotection. We then define the interactions with other neurotransmitters, neuromodulators, and gliotransmitters. Finally, we describe their fine-tuning on the network level and the behavioral relevance of their modulation. We believe that a better understanding of the sequence and nature of events that drive neuro-glial communication holds promise for the development of new treatment strategies that could, in a context- and time-dependent manner, modulate the action of specific chemokines to promote brain repair and reduce the neurological impairment.

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Insight into the roles of CCR5 in learning and memory in normal and disordered states

Cited by 37 publications

References 91 publications

Identification of Molecular Signatures and Candidate Drugs in Vascular Dementia by Bioinformatics Analyses

Identification of Molecular Signatures and Candidate Drugs in Vascular Dementia by Bioinformatics Analyses

Therapeutic Mechanism and Key Alkaloids of Uncaria rhynchophylla in Alzheimer’s Disease From the Perspective of Pathophysiological Processes

Cellular, synaptic, and network effects of chemokines in the central nervous system and their implications to behavior

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