Sterile systemic inflammation may contribute to neuroinflammation and accelerate the progression of neurodegenerative diseases. The double-stranded RNA-dependent protein kinase (PKR) is a key signaling molecule that regulates immune responses by regulating macrophage activation, various inflammatory pathways, and inflammasome formation. This study aims to study the role of PKR in regulating sterile systemic inflammation-triggered neuroinflammation and cognitive dysfunctions. Here, the laparotomy mouse model was used to study neuroimmune responses triggered by sterile systemic inflammation. Our study revealed that genetic deletion of PKR in mice potently attenuated the laparotomy-induced peripheral and neural inflammation and cognitive deficits. Furthermore, intracerebroventricular injection of rAAV-DIO-PKR-K296R to inhibit PKR in cholinergic neurons of ChAT-IRES-Cre-eGFP mice rescued the laparotomy-induced changes in key metabolites of brain glucose metabolism, particularly the changes in phosphoenolpyruvate and succinate levels, and cognitive impairment in short-term and spatial working memory. Our results demonstrated the critical role of PKR in regulating neuroinflammation, brain glucose metabolism and cognitive dysfunctions in a peripheral inflammation model. PKR could be a novel pharmacological target for treating systemic inflammation-induced neuroinflammation and cognitive dysfunctions.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893411 | PMC |
| http://dx.doi.org/10.3389/fimmu.2025.1469737 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
PKR modulates sterile systemic inflammation-triggered neuroinflammation and brain glucose metabolism disturbances.
Front Immunol
March 2025
Laboratory of Neurodegenerative Diseases, School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China.
Sterile systemic inflammation may contribute to neuroinflammation and accelerate the progression of neurodegenerative diseases. The double-stranded RNA-dependent protein kinase (PKR) is a key signaling molecule that regulates immune responses by regulating macrophage activation, various inflammatory pathways, and inflammasome formation. This study aims to study the role of PKR in regulating sterile systemic inflammation-triggered neuroinflammation and cognitive dysfunctions.
View Article and Find Full Text PDFCyclophosphamide treatment with a comparison in both pediatric rheumatology and pediatric nephrology practices.
Pediatr Rheumatol Online J
March 2025
Department of Pediatric Nephrology, Gazi University Faculty of Medicine, Ankara, Turkey.
Background: Cyclophosphamide (CYC) is an inactive alkylating agent that transforms the alkyl radicals into other molecules and is used in combination with systemic corticosteroids in the treatment of many childhood rheumatic diseases, such as systemic lupus erythematosus (SLE), and ANCA-associated vasculitis (AAV). In recent years, rituximab (RTX), a B-cell-targeting anti-CD20 monoclonal antibody, has emerged as a new alternative treatment modality over CYC for induction therapy of childhood-onset rheumatic diseases. Clinicians adopt different practices for using CYC particularly in relation to indications, posology, pre-treatment laboratory work-up, post-treatment follow-up, and screening pre- and post-treatment vaccination status.
View Article and Find Full Text PDFThe Discovery of Gadopiclenol: An Example of Rational Drug Design?
Invest Radiol
March 2025
From the Laboratoire de Génomique, Bioinformatique et Chimie Moléculaire (EA 7528), Equipe Chimie Moléculaire, Conservatoire National des Arts et Métiers, Paris, France.
Gadopiclenol was initially developed as a high-relaxivity, nonspecific magnetic resonance imaging contrast agent to enhance image quality and thereby improve diagnostics. This design required a highly demanding Drug Target Profile, addressing not only relaxivity but also factors such as physicochemical properties of the injectable solution (viscosity, osmolality, heat sterilization compatibility), pharmacokinetics and toxicity, particularly related to the stability of the complex. These considerations led to a multiparametric molecular design based on a gadolinium complex characterized by the following features: (1) a macrocyclic, nonionic structure based on the PCTA framework with 2 water molecules in the inner sphere; (2) the introduction of steric constraints around the gadolinium to enhance stability and reduce relaxivity quenching by endogenous ions; (3) slowed rotational diffusion due to gadolinium's position at the center of the complex; and (4) the incorporation of 3 hydrophilic amino polyol pendant arms to ensure aqueous solubility, reduce binding with endogenous proteins, and enhance product safety.
View Article and Find Full Text PDFDeciphering the association between the Life's Essential 8 and infertility: insights into depression, inflammation, and metabolic mediation.
Front Endocrinol (Lausanne)
March 2025
NHC Key Laboratory of Male Reproduction and Genetics, Guangdong Provincial Reproductive Science Institute (Guangdong Provincial Fertility Hospital), Guangzhou, China.
Background: The Life's Essential 8 (LE8) score has been associated with various health outcomes, but its relationship with female infertility remains unclear.
Methods: This study investigated the relationship between LE8 and infertility in women aged 20-45 years using the National Health and Nutrition Examination Survey (NHANES) data from 2013 to 2020. Weighted multifactorial logistic regression models were utilized to examine the association between the LE8 factors and their two subgroups [health behavior score (HBS) and health factor score (HFS)], as well as depressive status and infertility.
Acute Generalized Exanthematous Pustulosis in a 76-year-Old Man With Neuroendocrine Carcinoma of the Lung, Responsive to Ixekizumab.
Clin Cosmet Investig Dermatol
February 2025
Guangzhou Dermatology Hospital, Guangzhou, Guangdong, People's Republic of China.
Acute generalized exanthematous pustulosis (AGEP) is a rare, painful, and pruritic drug-induced rash characterized by sterile pustules on an erythematous base, followed by desquamation. While commonly induced by antibiotics, cases associated with antineoplastic drugs have become more frequent in recent years. Here, we report a 76-year-old Chinese male with lung large-cell neuroendocrine carcinoma who developed erythema and pustules on his left lower leg, which spread to the trunk and limbs after the fourth cycle of immunotherapy and chemotherapy.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!