Neurotrophin Signaling Impairment by Viral Infections in the Central Nervous System

Böhmwald, Karen; Andrade, Catalina A; Mora, Valentina P.; Muñoz, José T.; Ramírez, Rodrigo; Rojas, Maria Fernanda; Kalergis, Alexis M.

doi:10.3390/ijms23105817

Cited by 17 publications

(12 citation statements)

References 160 publications

(345 reference statements)

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“…NGFR present on the cell surface reportedly recognizes the NGF, BDNF, NT-3, and NT-4 signals that regulate various biological functions of the cells [21,22]. The cell-to-cell communication assay conducted in the present study revealed that NGF-NGFR communication was the only signal in the tumor tissues of HCC patients.…”

Section: Discussionmentioning

confidence: 51%

NGF-NGFR communication inefficiency induces T Cell exhaustion impairing PD-1 immunotherapy in hepatocellular carcinoma

Yang

et al. 2023

Preprint

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The number of T cells that infiltrate tumor tissues in hepatocellular carcinoma (HCC) is significantly low. The molecular mechanism underlying T cell proliferation in tumor tissues is poorly understood. The present study revealed that during the process of T cell infiltration from adjacent tissues to tumor tissues, the NGF-NGFR communication inefficiency occurred in the tumor tissues of HCC patients. Importantly, the tumor cell-secreted NGF interacted with NGFR on the membranes of the infiltrated T cells, which promoted proliferation of these cells through mitotic spindle signal activation. Mechanistically, the mitotic spindle signal activation promoted the proliferation was mediated by the HDAC1 unclear trans-localization-inhibited PREX1 expression. Further, PD-1 mAb acted synergistically with the NGF-NGFR communication to suppress tumor progression in both mouse model and HCC patients. In addition, NGF–NGFR communication was positively correlated with the PD-1/PDL-1 expression. However, NGF and NGFR expressions were low in tumor tissues, which was responsible for the incursive clinicopathological features and the disappointing prognosis in HCC patients. Collectively, the results suggested that NGF-NGFR communication inefficiency impaired PD-1 mAb immunotherapy and could, therefore, be utilized as a novel therapeutic target in the treatment of HCC patients in clinical practice.

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Section: Discussionmentioning

confidence: 51%

NGF-NGFR communication inefficiency induces T Cell exhaustion impairing PD-1 immunotherapy in hepatocellular carcinoma

Yang

et al. 2023

Preprint

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“…NGFR present on the cell surface reportedly recognizes the NGF, BDNF, NT-3, and NT-4 signals that regulate various biological functions of the cells. 22,23 The cell-to-cell communication assay conducted in the present study revealed that NGF-NGFR communication was the only signal in the tumor tissues of HCC patients. This result indicated no possibility of communication between NGFR and the other three ligands.…”

Section: Discussionmentioning

confidence: 58%

Heterogeneity‐induced NGF‐NGFR communication inefficiency promotes mitotic spindle disorganization in exhausted T cells through PREX1 suppression to impair the anti‐tumor immunotherapy with PD‐1 mAb in hepatocellular carcinoma

Wang,

Yang,

Shi

et al. 2024

Cancer Medicine

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BackgroundThe mechanism of decreased T cells infiltrating tumor tissues in hepatocellular carcinoma is poorly understood.MethodsCells were separated from the single‐cell RNA‐sequence dataset of hepatocellular carcinoma patients (GSE149614) for cell‐cell communication. Flow cytometry, EDU staining, H3‐Ser28 staining, confocal immunofluorescence staining, western blotting and naked microsubcutaneous tumors were performed for the mechanism of NGF‐NGFR promoting proliferation.ResultsThe present study has revealed that during the process of T‐cell infiltration from adjacent tissues to tumor tissues, an inefficiency in NGF‐NGFR communication occurs in the tumor tissues. Importantly, NGF secreted by tumor cells interacts with NGFR present on the membranes of the infiltrated T cells, thereby promoting the proliferation through the activation of mitotic spindle signals. Mechanistically, the mediation of mitotic spindle signal activation promoting proliferation is executed by HDAC1‐mediated inhibition of unclear trans‐localization of PREX1. Furthermore, PD‐1 mAb acts synergistically with the NGF‐NGFR communication to suppress tumor progression in both mouse models and HCC patients. Additionally, NGF‐NGFR communication was positively correlates with the PD‐1/PDL‐1 expression. However, expressions of NGF and NGFR are low in tumor tissues, which is responsible for the invasive clinicopathological features and the disappointing prognosis in HCC patients.ConclusionInefficiency in NGF‐NGFR communication impairs PD‐1 mAb immunotherapy and could thus be utilized as a novel therapeutic target in the treatment of HCC patients in clinical practice.

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“…Several studies shed light on how viral infections and vaccines affect the central nervous system. Bohmwald et al (2022) highlight the importance of neurotrophins in the CNS function, with viral infections impairing their signaling [ 36 ]. Azoulay et al (2020) underscore BDNF's role during recovery from SARS-CoV-2 infection [ 37 ], while Demir et al (2022) delve into COVID-19’s prolonged cognitive effects and the possible involvement of BDNF [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Prenatal Exposure to COVID-19 mRNA Vaccine BNT162b2 Induces Autism-Like Behaviors in Male Neonatal Rats: Insights into WNT and BDNF Signaling Perturbations

Erdogan,

Gurbuz,

Bozkurt

et al. 2024

Neurochem Res

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The COVID-19 pandemic catalyzed the swift development and distribution of mRNA vaccines, including BNT162b2, to address the disease. Concerns have arisen about the potential neurodevelopmental implications of these vaccines, especially in susceptible groups such as pregnant women and their offspring. This study aimed to investigate the gene expression of WNT, brain-derived neurotrophic factor (BDNF) levels, specific cytokines, m-TOR expression, neuropathology, and autism-related neurobehavioral outcomes in a rat model. Pregnant rats received the COVID-19 mRNA BNT162b2 vaccine during gestation. Subsequent evaluations on male and female offspring included autism-like behaviors, neuronal counts, and motor performance. Molecular techniques were applied to quantify WNT and m-TOR gene expressions, BDNF levels, and specific cytokines in brain tissue samples. The findings were then contextualized within the extant literature to identify potential mechanisms. Our findings reveal that the mRNA BNT162b2 vaccine significantly alters WNT gene expression and BDNF levels in both male and female rats, suggesting a profound impact on key neurodevelopmental pathways. Notably, male rats exhibited pronounced autism-like behaviors, characterized by a marked reduction in social interaction and repetitive patterns of behavior. Furthermore, there was a substantial decrease in neuronal counts in critical brain regions, indicating potential neurodegeneration or altered neurodevelopment. Male rats also demonstrated impaired motor performance, evidenced by reduced coordination and agility. Our research provides insights into the effects of the COVID-19 mRNA BNT162b2 vaccine on WNT gene expression, BDNF levels, and certain neurodevelopmental markers in a rat model. More extensive studies are needed to confirm these observations in humans and to explore the exact mechanisms. A comprehensive understanding of the risks and rewards of COVID-19 vaccination, especially during pregnancy, remains essential.

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Neurotrophin Signaling Impairment by Viral Infections in the Central Nervous System

Cited by 17 publications

References 160 publications

NGF-NGFR communication inefficiency induces T Cell exhaustion impairing PD-1 immunotherapy in hepatocellular carcinoma

NGF-NGFR communication inefficiency induces T Cell exhaustion impairing PD-1 immunotherapy in hepatocellular carcinoma

Heterogeneity‐induced NGF‐NGFR communication inefficiency promotes mitotic spindle disorganization in exhausted T cells through PREX1 suppression to impair the anti‐tumor immunotherapy with PD‐1 mAb in hepatocellular carcinoma

Prenatal Exposure to COVID-19 mRNA Vaccine BNT162b2 Induces Autism-Like Behaviors in Male Neonatal Rats: Insights into WNT and BDNF Signaling Perturbations

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